Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.191
Filtrar
1.
Medicine (Baltimore) ; 99(40): e22337, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019410

RESUMO

At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of ß-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Jejum/metabolismo , Resistência à Insulina/fisiologia , Adolescente , Adulto , Peptídeo C/sangue , Criança , Feminino , Frutosamina/sangue , Hemoglobina A Glicada/análise , Índice Glicêmico , Humanos , Insulina/sangue , Masculino , Albumina Sérica/análise , Adulto Jovem
2.
Intern Med ; 59(18): 2229-2235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32938850

RESUMO

Objective The measurement of C-peptide immunoreactivity (CPR) is essential for evaluating the pancreatic ß-cell function and selecting appropriate therapeutic agents in patients with diabetes mellitus. The meal tolerance test (MTT) is simple to administer physiological insulin-stimulating test. Previous studies have reported that several CPR-related indices are useful markers for predicting insulin requirement in type 2 diabetes. In the present study, we investigated the serum CPR response during the MTT in hospitalized patients with type 2 diabetes mellitus in order to clarify the clinical utility of the MTT. Methods We performed the MTT using a test meal with timed measurements of the serum CPR level based on the oral glucose tolerance test over 180 minutes and tested the correlation of various CPR-related indices and clinical factors in patients with type 2 diabetes mellitus. Patients The subjects were patients with type 2 diabetes mellitus who had been admitted to our hospital for diabetes management and education. The final study population consisted of 68 patients. Results The fasting CPR level was correlated with the 24-hour urinary CPR excretion and body mass index. The serum CPR level at 120 minutes in the MTT was strongly correlated with the area under the curve of CPR during the MTT. The patients who needed insulin therapy at 6 months after hospitalization showed a significant lower incremental CPR value from 0 to 120 minutes in the MTT than those who did not need insulin therapy. Conclusion The plasma C-peptide levels at 0 and 120 minutes in the MTT provide essential information for the clinical management of patients with type 2 diabetes mellitus.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Técnicas de Diagnóstico Endócrino , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Células Secretoras de Insulina/fisiologia , Masculino , Refeições , Carne , Pessoa de Meia-Idade , Período Pós-Prandial
3.
PLoS One ; 15(5): e0231190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369480

RESUMO

OBJECTIVE: For those with type 2 diabetes mellitus (T2DM), impact of short-term high-dose glucocorticoid exposure on beta-cell function is unknown. This study aims to compare the impact on beta-cell function and insulin resistance of prednisone 40 mg between adults with newly diagnosed T2DM and healthy adults. METHODS: Five adults with T2DM and five healthy adults, all between 18-50 years, were enrolled. T2DM diagnosis was less than one year prior, HbA1c<75 mmol/mol (9.0%), with metformin treatment only. Pre- and post-therapy testing included 75-g oral glucose tolerance, plasma glucose, C-peptide, and insulin. Intervention therapy was prednisone 40mg daily for 3 days. RESULTS: Upon therapy completion, HOMA-IR did not increase or differ between groups. Percentile difference for HOMA-%B and insulinogenic index in those with T2DM was significantly lower statistically (50.4% and 69.2% respectively) compared to healthy subjects (19% and 32.2%). CONCLUSIONS: Contrary to the assumption that insulin resistance is the main driver of glucocorticoid-induced hyperglycemia, results indicate that decreased beta-cell insulin secretion is the more likely cause in those with T2DM. This is evidenced by significant drops in C-peptide AUC and HOMA-%B and increased glucose AUC in T2DM group only. These results may be caused by increased beta-cell fragility along with reduced recovery ability after glucocorticoid exposure. ClinicalTrials.gov NCT03661684.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Células Secretoras de Insulina/efeitos dos fármacos , Prednisona/farmacologia , Adulto , Glicemia/análise , Peptídeo C/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem
4.
Clin Sci (Lond) ; 134(9): 1081-1094, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32352510

RESUMO

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.


Assuntos
Glicemia/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insuficiência Cardíaca/etiologia , Período Pós-Prandial/fisiologia , Idoso , Animais , Peptídeo C/sangue , Feminino , Intolerância à Glucose/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Fragmentos de Peptídeos/sangue , Ratos Wistar
5.
Med Sci Sports Exerc ; 52(7): 1449-1455, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028458

RESUMO

PURPOSE: We aimed to determine the immediacy of exercise intervention on liver-specific metabolic processes in nonalcoholic fatty liver disease. METHODS: We undertook a short-term (7-d) exercise training study (60 min·d treadmill walking at 80%-85% of maximal heart rate) in obese adults (N = 13, 58 ± 3 yr, 34.3 ± 1.1 kg·m, >5% hepatic lipid by H-magnetic resonance spectroscopy). Insulin sensitivity index was estimated by oral glucose tolerance test using the Soonthorpun model. Hepatic insulin extraction (HIE) was calculated as the molar difference in area under the curve (AUC) for insulin and C-peptide (HIE = 1 - (AUCInsulin/AUCC-Pep)). RESULTS: The increases in HIE, V˙O2max, and insulin sensitivity index after the intervention were 9.8%, 9.8%, and 34%, respectively (all, P < 0.05). Basal fat oxidation increased (pre: 47 ± 6 mg·min vs post: 65 ± 6 mg·min, P < 0.05) and carbohydrate oxidation decreased (pre: 160 ± 20 mg·min vs post: 112 ± 15 mg·min, P < 0.05) with exercise training. After the intervention, HIE correlated positively with adiponectin (r = 0.56, P < 0.05) and negatively with TNF-α (r = -0.78, P < 0.001). CONCLUSIONS: By increasing HIE along with peripheral insulin sensitivity, aerobic exercise training rapidly reverses some of the underlying physiological mechanisms associated with nonalcoholic fatty liver disease, in a weight loss-independent manner. This reversal could potentially act through adipokine-related pathways.


Assuntos
Exercício Físico/fisiologia , Insulina/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Glicemia/metabolismo , Peptídeo C/sangue , Metabolismo dos Carboidratos , Peptídeo 1 Semelhante ao Glucagon/sangue , Frequência Cardíaca , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , Obesidade/metabolismo , Consumo de Oxigênio
6.
Cleve Clin J Med ; 87(2): 100-108, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015063

RESUMO

The classification of diabetes mellitus in 2020 still starts with 2 major types, ie, type 1 and type 2, but each of these now includes a few uncommon variants. Understanding the many faces of the diabetes syndrome can make a difference in how clinicians select glucose-lowering therapy.


Assuntos
Autoanticorpos/sangue , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hiperglicemia/etiologia , Diabetes Autoimune Latente em Adultos/diagnóstico , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/diagnóstico , Diabetes Autoimune Latente em Adultos/sangue , Fenótipo
7.
Metabolism ; 105: 154175, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045582

RESUMO

PURPOSE: Abnormal glucagon concentrations are a feature of prediabetes but it is uncertain if α-cell dysfunction contributes to a longitudinal decline in ß-cell function. We therefore sought to determine if a decline in ß-cell function is associated with a higher nadir glucagon in the postprandial period or with higher fasting glucagon. METHODS: This was a longitudinal study in which 73 non-diabetic subjects were studied on 2 occasions 6.6 ±â€¯0.3 years apart using a 2-hour, 7-sample oral glucose tolerance test. Disposition Index (DI) was calculated using the oral minimal model applied to the measurements of glucose, insulin, C-peptide concentrations during the studies. We subsequently examined the relationship of glucagon concentrations at baseline with change in DI (used as a measure of ß-cell function) after adjusting for changes in weight and the baseline value of DI. RESULTS: After adjusting for covariates, nadir postprandial glucagon concentrations were not associated with changes in ß-cell function as quantified by DI. On the other hand, fasting glucagon concentrations during the baseline study were inversely correlated with longitudinal changes in DI. CONCLUSIONS: Defects in α-cell function, manifest as elevated fasting glucagon, are associated with a subsequent decline in ß-cell function. It remains to be ascertained if abnormal α-cell function contributes directly to loss of ß-cell secretory capacity in the pathogenesis of type 2 diabetes.


Assuntos
Glucagon/sangue , Células Secretoras de Insulina/fisiologia , Adulto , Glicemia/análise , Peptídeo C/sangue , Jejum , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pâncreas/citologia , Pâncreas/crescimento & desenvolvimento , Período Pós-Prandial , Estado Pré-Diabético/metabolismo
8.
Drug Test Anal ; 12(3): 382-390, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930697

RESUMO

The quantification of peptide hormones by means of liquid chromatography (LC) coupled to mass spectrometry (MS) or other techniques (e.g. immunoassays) has been a challenging task in modern analytical chemistry. Especially for insulin, its synthetic analogs, and C-peptide, reliable determinations are urgently needed due to their diagnostic value in the management of diabetes and insulin resistance and because of the illicit use of insulin as a performance-enhancing agent in professional sports or as an effective toxin in forensic toxicology. The concomitant measurement of C-peptide and insulin offers an established tool for the diagnostic workup of hypoglycemia (endogenous vs. exogenous hyperinsulinemia), characterizing hepatic insulin clearance, and the assessment of beta-cell function (insulin secretion). Thus, the present approach offers the possibility to determine human insulin and its synthetic analogs (lispro, glulisine, aspart, glargine metabolite, degludec, detemir, porcine, and bovine) and C-peptide simultaneously after sample preparation utilizing protein precipitation and a mixed-mode cation-exchange solid-phase extraction, and subsequent detection by LC-high resolution MS. The method was fully validated regarding the following parameters: specificity, limit of detection (0.2 ng/mL), limit of quantification (0.6 ng/mL), recovery (40-90%), accuracy (78-128%), linearity, precision (< 21%), carry over, robustness, and matrix effects. The proof-of-concept was shown by analyzing authentic plasma samples from adults with class II obesity and prediabetes collected in the course of an oral glucose tolerance test. All sample preparation steps were controlled by two stable isotope-labeled internal standards, namely [[2 H10 ] Leu B6, B11, B15, B17 ]-insulin, and [[13 C6 ] Leu 26, 30 ] C-peptide.


Assuntos
Peptídeo C/sangue , Insulina/análogos & derivados , Insulina/sangue , Cromatografia Líquida/métodos , Feminino , Humanos , Limite de Detecção , Masculino , Obesidade/sangue , Sensibilidade e Especificidade , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
9.
Diabetes Res Clin Pract ; 160: 108027, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958476

RESUMO

AIMS: Whether fasting C-peptide can be a potential indicator for nonalcoholic fatty liver disease (NAFLD) in obese children is unknown. This study aimed to assess whether fasting C-peptide represented a risk factor for NAFLD. METHODS: A total of 520 obese children (376 male, 144 female) aged 3.4-17.1 years were divided into two groups, obese with NAFLD and non-NAFLD, according to hepatic ultrasound results. Fasting plasma glucose, fasting C-peptide, hemoglobin A1c, renal function, liver function, blood lipid, fasting insulin and blood routine indices were measured. Insulin resistance by homoeostasis model (HOMA-IR) was calculated. RESULTS: Compared with the non-NAFLD group, the obese children with NAFLD had higher fasting C-peptide, fasting insulin and HOMA-IR (P < 0.001). Stepwise multiple logistic regression models showed that fasting C-peptide (odds ratio: OR = 2.367) was independent indicator of the presence of NAFLD in obese children as well as white blood cell (OR = 1.113), albumin (OR = 1.124), alanine aminotransferase (OR = 1.030), triglycerides (OR = 1.335), and waist circumference (OR = 1.047). Furthermore, after adjustment for confounding variables, the prevalence of NAFLD in obese children was significantly higher according to increased serum fasting C-peptide levels. The adjusted OR for NAFLD according to fasting C-peptide tertiles were 1.00 (as references), 1.896(1.045-3.436), and 4.169(1.822-9.537). CONCLUSION: Our data suggested that obese children with high level of fasting C-peptide had an increased risk for developing NAFLD.


Assuntos
Peptídeo C/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade Pediátrica/complicações , Criança , Jejum , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco
10.
Am J Med Sci ; 359(1): 32-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31902439

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is a nonischemic myocardial disorder characterized by metabolic disturbances and oxidative stress in diabetic patients. The present paper aims to determine the protective effect of the phlebotrophic drug, diosmin, on DCM in a model of high-fat diet-fed and streptozotocin-induced type 2 diabetes in the rat. MATERIALS AND METHODS: The animals were divided into 4 groups (8 rats/group) as follows: vehicle-treated nondiabetic control group, vehicle-treated diabetic group, diosmin (50 mg/kg)-treated diabetic group and diosmin (100 mg/kg)-treated diabetic group. Treatment was given once daily orally by gavage for 6 weeks. Oxidant and antioxidant stress markers, inflammatory markers and proapoptotic and antiapoptotic gene expression using quantified real-time polymerase chain reaction were investigated. RESULTS: Diosmin treatment in diabetic rats lowered elevated blood glucose levels, homeostatic model assessment for insulin resistance, cardiac creatine kinase and lactate dehydrogenase enzymes, cardiac malondialdehyde and nitric oxide. Moreover, diosmin increased plasma insulin and c-peptide levels, cardiac glutathione content, superoxide dismutase, catalase and glutathione S-transferase activities. Also, diosmin treatment significantly (P < 0.05) lowered the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), down-regulated cardiac Bcl-2-associated X protein and caspase 3 and 9 and up-regulated B-cell lymphoma 2 mRNA expression levels. CONCLUSIONS: Diosmin may have a sizeable therapeutic potential in the treatment of DCM due to antidiabetic, antioxidative stress, anti-inflammatory and antiapoptotic effects. Detailed studies are needed to disclose the precise mechanisms motivating the protective effect of diosmin .


Assuntos
Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Diosmina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores/sangue , Glicemia , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diosmina/administração & dosagem , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase , Insulina/sangue , Resistência à Insulina , Ratos
11.
Int J Mol Sci ; 21(2)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963760

RESUMO

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic ß-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive ß-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal-regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.


Assuntos
Peptídeo C/sangue , Doenças Vasculares/prevenção & controle , Humanos , Sistema de Sinalização das MAP Quinases , Óxido Nítrico/metabolismo , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo
12.
Biochem Med (Zagreb) ; 30(1): 010802, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839727

RESUMO

Introduction: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. Case description: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use.


Assuntos
Analgésicos Opioides/efeitos adversos , Hipoglicemia/diagnóstico , Tramadol/efeitos adversos , Analgésicos Opioides/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Glucose/administração & dosagem , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/etiologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Tramadol/uso terapêutico
13.
Diabetes Metab Syndr ; 13(6): 3099-3104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31785503

RESUMO

AIMS: To determine beta cell reserves of patients with type 2 diabetes who are treated with insulin by using fasting C-peptide concentrations and to investigate the clinical features related to C-peptide concentrations. MATERIALS AND METHODS: Patients with type 2 diabetes, who were using insulin as monotherapy or in combination therapy, were divided into three groups; those with an insufficient beta cell reserve (C-peptide: <0.5 ng/mL), borderline reserve (C-peptide: 0.5-2 ng/mL) and sufficient reserve (C-peptide:> 2 ng/mL). RESULTS: In the 249 patients (mean age, 61.77 ± 9.34 years; 40.6% male), the mean duration of diabetes was 13.9 ± 8.43 years. The mean HbA1c concentrations, fasting glucose and C-peptide concentrations were 8.88 ± 1.87%, 184.29 ± 77.88 mg/dL and 1.95 ± 1.37 ng/mL, respectively. Fifty-seven percent of patients (n = 142) had a borderline beta cell reserve and 37% (n = 92) had high C-peptide concentrations. Only 6% of patients (n = 15) had an insufficient beta cell reserve. C-peptide levels were positively correlated with waist circumference (r: 0.282; p = 0.001), hip circumference (r: 0.251; p = 0.001), body mass index (r: 0.279; p = 0.001), fasting glucose concentrations (r: 0.309; p = 0.001) and triglyceride concentrations (r: 0.358; p = 0.001). CONCLUSION: In this study, almost all patients with type 2 diabetes using insulin were found to have sufficient or borderline beta cell reserves and insulin resistance-related parameters were prominent in those with adequate beta cell reserve. CLINICAL TRIALS NO: NCT04005261.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Insulina/uso terapêutico , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobina A Glicada/análise , Humanos , Células Secretoras de Insulina/fisiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Diabetes Res Clin Pract ; 158: 107894, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669629

RESUMO

AIMS: Little information is published on diabetes in young people in Bangladesh. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting Bangladeshi children and adolescents <22 years of age. METHODS: The study was conducted at Bangladesh Institute of Research and Rehabilitation of Diabetes, Endocrine and Metabolic Disorders (BIRDEM) in Dhaka. One hundred subjects aged <22 years at diagnosis were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, and autoantibodies against glutamic acid decarboxylase 65 (GADA) and islet antigen-2 (IA-2A) were measured. High-resolution DNA genotyping was performed for HLA-DRB1. RESULTS: Eighty-four subjects were clinically diagnosed as type 1 diabetes (T1D), seven as type 2 diabetes (T2D), and nine as fibrocalculous pancreatic disease (FCPD). Of the 84 with T1D, 37 (44%) were males and 47 (56%) females, with median age at diagnosis 13 years (y) (range 1.6-21.7) and peak age at onset 12-15 years. 85% of subjects were assessed within one month of diagnosis and all within eleven months. For subjects diagnosed with T1D, mean C-peptide was 0.46 ±â€¯0.22 nmol/L (1.40 ±â€¯0.59 ng/mL), with 9 (10.7%) IA-2A positive, 22 (26%) GADA positive, and 5 (6%) positive for both autoantibodies. Analysis of HLA-DRB1 genotypes revealed locus-level T1D association (p = 6.0E-05); DRB1*04:01 appeared predisposing (p < 3.0E-06), and DRB1*14:01 appeared protective (p = 1.7E-02). CONCLUSIONS: Atypical forms of T1D appear to be more common in young people in Bangladesh than in European populations. This will be helpful in guiding more specific assessment at onset and potentially, expanding treatment options.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/genética , Cadeias HLA-DRB1/genética , Adolescente , Adulto , Bangladesh , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
15.
Am J Physiol Endocrinol Metab ; 317(5): E805-E819, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479304

RESUMO

Inhibition of insulin-degrading enzyme (IDE) has been proposed as a possible therapeutic target for type 2 diabetes treatment. However, many aspects of IDE's role in glucose homeostasis need to be clarified. In light of this, new preclinical models are required to elucidate the specific role of this protease in the main tissues related to insulin handling. To address this, here we generated a novel line of mice with selective deletion of the Ide gene within pancreatic beta-cells, B-IDE-KO mice, which have been characterized in terms of multiple metabolic end points, including blood glucose, plasma C-peptide, and intraperitoneal glucose tolerance tests. In addition, glucose-stimulated insulin secretion was quantified in isolated pancreatic islets and beta-cell differentiation markers and insulin secretion machinery were characterized by RT-PCR. Additionally, IDE was genetically and pharmacologically inhibited in INS-1E cells and rodent and human islets, and insulin secretion was assessed. Our results show that, in vivo, life-long deletion of IDE from beta-cells results in increased plasma C-peptide levels. Corroborating these findings, isolated islets from B-IDE-KO mice showed constitutive insulin secretion, a hallmark of beta-cell functional immaturity. Unexpectedly, we found 60% increase in Glut1 (a high-affinity/low-Km glucose transporter), suggesting increased glucose transport into the beta-cell at low glucose levels, which may be related to constitutive insulin secretion. In parallel, IDE inhibition in INS-1E and islet cells resulted in impaired insulin secretion after glucose challenge. We conclude that IDE is required for glucose-stimulated insulin secretion. When IDE is inhibited, insulin secretion machinery is perturbed, causing either inhibition of insulin release at high glucose concentrations or constitutive secretion.


Assuntos
Secreção de Insulina/genética , Células Secretoras de Insulina/metabolismo , Insulisina/metabolismo , Animais , Glicemia/metabolismo , Peptídeo C/sangue , Feminino , Glucose/farmacologia , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 1/metabolismo , Homeostase , Humanos , Insulisina/genética , Masculino , Camundongos , Camundongos Knockout , RNA Interferente Pequeno/farmacologia , Ratos
16.
PLoS One ; 14(9): e0222598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536546

RESUMO

OBJECTIVE: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia. RESULTS: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level. CONCLUSION: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM.


Assuntos
Translocação Bacteriana/fisiologia , Diabetes Mellitus Tipo 2/microbiologia , Proteínas da Fase Aguda , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Peptídeo C/sangue , Proteína C-Reativa/metabolismo , Proteínas de Transporte/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Endotoxemia/sangue , Endotoxemia/metabolismo , Endotoxemia/microbiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-6/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
J Diabetes Res ; 2019: 1747684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485449

RESUMO

Introduction: Urinary C-peptide creatinine ratio (UCPCR) is used as a marker of endogenous insulin secretion. This study aims to assess the effectiveness of UCPCR for distinguishing between type 1 diabetes (T1DM) and non-T1DM (monogenic diabetes and T2DM) and predicting therapeutic choices in type 2 diabetes (T2DM) patients. Methods: Twenty-three patients with genetically confirmed monogenic diabetes (median age 35.0 years (interquartile range 30.0-47.0), 13 (56.5%) men), 56 patients with T1DM (median age 46.0 years (interquartile range 26.5-59.5), 28 (50.0%) men), 136 patients with T2DM (median age 53.0 years (interquartile range 42.0-60.0), 87 (64.0%) men), and 59 healthy subjects (median age 36.0 years (30.0-42.0), 26 (44.1%) men) were included. UCPCR was collected in the morning. Receiver operating characteristic (ROC) curves were used to identify optimal UCPCR cut-off values to differentiate T1DM from non-T1DM. This UCPCR cut-off was used to divide T2DM patients into two groups, and the two groups were compared. Results: The UCPCR was lower in patients with T1DM compared with T2DM, monogenic diabetes, and healthy subjects, while the UCPCR was similar in T2DM and monogenic diabetes. A UCPCR cut-off of ≥0.21 nmol/mmol distinguished between monogenic diabetes and T1DM (area under the curve [AUC], 0.949) with 87% sensitivity and 93% specificity. UCPCR ≥ 0.20 nmol/mmol had 82% sensitivity and 93% specificity for distinguishing between T2DM and T1DM, with an AUC of 0.932. UCPCR was not reliable for distinguishing between monogenic diabetes and T2DM (AUC, 0.605). Twenty-five of 136 (18.4%) T2DM patients had UCPCR ≤ 0.20 nmol/mmol. Compared with T2DM patients with a UCPCR > 0.20 nmol/mmol, T2DM patients with UCPCR ≤ 0.20 nmol/mmol had a lower serum C-peptide (fasting C-peptide, 0.39 nmol/L vs. 0.66 nmol/L, P < 0.001; postprandial C-peptide, 0.93 nmol/L vs. 1.55 nmol/L, P < 0.001), lower BMI (22.8 kg/m2 vs. 25.2 kg/m2, P = 0.006), and higher percentage of insulin or secretagogue therapy (92.0% vs. 59.5%, P = 0.002). Conclusions: UCPCR is a practical and noninvasive marker that can distinguish between TIDM and T2DM or monogenic diabetes. UCPCR ≤ 0.20 nmol/mmol reflects severe impaired beta cell function and the need for insulin or secretagogue therapy in T2DM patients.


Assuntos
Peptídeo C/urina , Creatinina/urina , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Peptídeo C/sangue , Estudos de Casos e Controles , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/classificação , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Urinálise
18.
NPJ Syst Biol Appl ; 5: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508240

RESUMO

Excessive increase in blood glucose level after eating increases the risk of macroangiopathy, and a method for not increasing the postprandial blood glucose level is desired. However, a logical design method of the dietary ingestion pattern controlling the postprandial blood glucose level has not yet been established. We constructed a mathematical model of blood glucose control by oral glucose ingestion in three healthy human subjects, and predicted that intermittent ingestion 30 min apart was the optimal glucose ingestion patterns that minimized the peak value of blood glucose level. We confirmed with subjects that this intermittent pattern consistently decreased the peak value of blood glucose level. We also predicted insulin minimization pattern, and found that the intermittent ingestion 30 min apart was optimal, which is similar to that of glucose minimization pattern. Taken together, these results suggest that the glucose minimization is achieved by suppressing the peak value of insulin concentration, rather than by enhancing insulin concentration. This approach could be applied to design optimal dietary ingestion patterns.


Assuntos
Glicemia/metabolismo , Ingestão de Alimentos/fisiologia , Glucose/metabolismo , Adulto , Peptídeo C/sangue , Dieta , Feminino , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Período Pós-Prandial/fisiologia
19.
Indian J Med Res ; 149(4): 479-488, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411171

RESUMO

Background & objectives: In contrast to Caucasians of European origin, the aetiology of diabetes mellitus (DM) in young adults in other ethnic groups, including Indians is likely to be heterogeneous and difficult to determine. This study was undertaken to determine the aetiology of diabetes in young Indian adults using a protocol-based set of simple clinical and investigation tools. Methods: In this prospective study, 105 Indian young adults with diabetes (age at onset 18-35 yr; duration <2 yr) were studied for a period of 1-3 years. Pancreatic imaging, fasting C-peptide, islet antibodies (against glutamic acid decarboxylase, tyrosine phosphatase and zinc transporter-8) and mitochondrial A3243G mutational analysis were performed in all patients. Four patients were screened for maturity-onset diabetes of the young (MODY) using next-generation sequencing. Results: Type 1 and type 2 diabetes mellitus (T1DM and T2DM) were equally frequent (40% each), followed by fibrocalculous pancreatic diabetes (FCPD, 15%). Less common aetiologies included MODY (2%), mitochondrial diabetes (1%) and Flatbush diabetes (2%). There was considerable phenotypic overlap between the main aetiological subtypes. Elevated islet antibodies were noted in 62 per cent of T1DM patients [positive predictive value (PPV) 84%; negative predictive value (NPV) 78%] while low plasma C-peptide (<250 pmol/l) was present in 56 per cent of T1DM patients [PPV 96% (after excluding FCPD), NPV 72%]. Using these tests and observing the clinical course over one year, a final diagnosis was made in 103 (99%) patients, while the diagnosis at recruitment changed in 23 per cent of patients. Interpretation & conclusions: The aetiology of diabetes in young adults was heterogeneous, with T1DM and T2DM being equally common. FCPD was also frequent, warranting its screening in Indian patients. Testing for islet antibodies and C-peptide in this age group had good PPV for diagnosis of T1DM.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Adulto , Idade de Início , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Índia/epidemiologia , Ilhotas Pancreáticas/patologia , Masculino , Pâncreas/patologia , Estudos Prospectivos , Adulto Jovem
20.
BMC Med ; 17(1): 165, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31438962

RESUMO

BACKGROUND: The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes. METHODS: C-peptide was measured in an untimed serum sample in the SDRNT1BIO cohort of 6076 Scottish people with clinically diagnosed type 1 diabetes or latent autoimmune diabetes of adulthood. Risk scores at loci previously associated with type 1 and type 2 diabetes were calculated from publicly available summary statistics. RESULTS: Prevalence of detectable C-peptide varied from 19% in those with onset before age 15 and duration greater than 15 years to 92% in those with onset after age 35 and duration less than 5 years. Twenty-nine percent of variance in C-peptide levels was accounted for by associations with male gender, late age at onset and short duration. The SNP heritability of residual C-peptide secretion adjusted for gender, age at onset and duration was estimated as 26%. Genotypic risk score for type 1 diabetes was inversely associated with detectable C-peptide secretion: the most strongly associated loci were the HLA and INS gene regions. A risk score for type 1 diabetes based on the HLA DR3 and DQ8-DR4 serotypes was strongly associated with early age at onset and inversely associated with C-peptide persistence. For C-peptide but not age at onset, there were strong associations with risk scores for type 1 and type 2 diabetes that were based on SNPs in the HLA region but not accounted for by HLA serotype. CONCLUSIONS: Persistence of C-peptide secretion varies widely in people clinically diagnosed as type 1 diabetes. C-peptide persistence is influenced by variants in the HLA region that are different from those determining risk of early-onset type 1 diabetes. Known risk loci for diabetes account for only a small proportion of the genetic effects on C-peptide persistence.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Adolescente , Adulto , Idade de Início , Estudos Transversais , Progressão da Doença , Feminino , Genótipo , Antígenos HLA-DQ/genética , Humanos , Masculino , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA