AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi...AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.展开更多
Atherosclerotic involvements are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis(CA) being a common risk-factor for prospective crisis of coronary artery diseases(CAD) an...Atherosclerotic involvements are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis(CA) being a common risk-factor for prospective crisis of coronary artery diseases(CAD) and/or cerebral infarction(CI) in DM subjects. From another point of view, several reports have supplied augmenting proof that hepatocyte growth factor(HGF) has a physiopathological part in DM involvements. HGF has been a mesenchymal-derived polyphenic factor which modulates development, motion, and morphosis of diverse cells, and has been regarded as a humor intermediator of epithelial-mesenchymal interplays. The serum concentrations of HGF have been elevated in subjects with CAD and CI, especially during the acute phase of both disturbances. In our study with 89 type 2 DM patients, the association between serum concentrationsof HGF and risk-factors for macrovascular complicationsinclusive of CA were examined. The average of serumHGF levels in the subjects was more elevated than thereference interval. The serum HGF concentrations associated positively with both intimal-media thickness(IMT)(r = 0.24, P = 0.0248) and plaque score(r = 0.27, P =0.0126), indicating a relationship between the elevatedHGF concentrations and advancement of CA involvements. Multivariate statistical analysis accentuated thatserum concentrations of HGF would be associated inde-pendently with IMT(standardized = 0.28, P = 0.0499).The review indicates what is presently known regardingserum HGF might be a new and meaningful biomarkerof macroangiopathy in DM subjects.展开更多
Progression of normal glucose tolerance(NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance(IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diab...Progression of normal glucose tolerance(NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance(IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus(type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options(lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed.展开更多
Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or ...Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.展开更多
Lipids play essential biological functions that include acting as components of biological membranes,energy storage,signaling,nutrients,transporters,enzyme activators,among others.Compared with the multiple research m...Lipids play essential biological functions that include acting as components of biological membranes,energy storage,signaling,nutrients,transporters,enzyme activators,among others.Compared with the multiple research methods to assess DNA,RNA,and protein content,location,and function in cells,there are relatively fewer methods to study lipids.Therefore,lipid-oriented mechanistic studies remain rare and challenging.展开更多
The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however mos...The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.展开更多
AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence(1979-2008) and morta...AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence(1979-2008) and mortality(1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality(ASMR) and incidence(ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer(PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel(Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software(Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma(IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio(1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years(2018) relative to 2008, particularly as a result of IHBD. CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.展开更多
Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) ident...Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.展开更多
Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting an...Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.展开更多
AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 DM.Mean age was 6...AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 DM.Mean age was 64.7 years,mean body mass index was 24.7 RESULTS Lower abdominal symptoms were found to be more frequent than those affecting the upper abdomen.Diabetic duration and medications showed associations with GI symptoms.We identified differences in peak prevalences of the five symptoms.Gastralgia(P=0.02vs 10-14 years)and total GI symptoms(P=0.01 and P=0.02 vs 5-9 years and 10-14 years,respectively)peaked at a diabetes duration of 15-19 years.Heartburn(P=0.004)and postprandial fullness(P=0.03)tended to increase with disease duration.Constipation and diarrhea showed bimodal peaks,with the first early and the second late(e.g.,P=0.03 at 15-19 years vs 10-14years for diarrhea)in the disease course.Finally,GI symptoms showed clustering that reflected the region of the GI tract affected,i.e.,constipation and diarrhea had similar frequencies(P<0.0001). CONCLUSION Our study highlights the importance of questioning patients about QOL impairment due to abdominal symptoms,especially in the early and the late periods of diabetes.展开更多
AIM:To investigate all patients referred to our center with non-responsive celiac disease (NRCD),to establish a cause for their continued symptoms.METHODS:We assessed all patients referred to our center with non-respo...AIM:To investigate all patients referred to our center with non-responsive celiac disease (NRCD),to establish a cause for their continued symptoms.METHODS:We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period.These individuals were investigated to establish the eitiology of their continued symptoms.The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement.They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion.A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible.Colonoscopy,lactulose hydrogen breath testing,pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted.Their clinical progress was followed over a minimum of 2 years.RESULTS:One hundred and twelve consecutive patients were referred with NRCD.Twelve were found not to have celiac disease (CD).Of the remaining 100 patients,45% were not adequately adhering to a strict gluten-free diet,with 24 (53%) found to be inadvertently ingesting gluten,and 21 (47%) admitting noncompliance.Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%.Refractory CD was diagnosed in 9%.Three of these were diagnosed with intestinal lymphoma.After 2 years,78 patients remained well,eight had continuing symptoms,and four had died.CONCLUSION:In individuals with NRCD,a remediable cause can be found in 90%:with continued gluten ingestion as the leading cause.We propose an algorithm for investigation.展开更多
Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for ...Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for a system of ordinary differential equations(ODEs)that represent the time course of plasma glucose and insulin concentrations during glucose tolerance test(GTT)in physiological studies is presented.The aim of this study was to explore how to interpret those laboratory glucose and insulin data as well as enhance the Ackerman mathematical model.Methods:Parameters estimation for a system of ODEs was performed by minimizing the sum of squared residuals(SSR)function,which quantifies the difference between theoretical model predictions and GTT's experimental observations.Our proposed perturbation search and multiple-shooting methods were applied during the estimating process.Results:Based on the Ackerman's published data,we estimated the key parameters by applying R-based iterative computer programs.As a result,the theoretically simulated curves perfectly matched the experimental data points.Our model showed that the estimated parameters,computed frequency and period values,were proven a good indicator of diabetes.Conclusion:The present paper introduces a computational algorithm to biomedical problems,particularly to endocrinology and metabolism fields,which involves two coupled differential equations with four parameters describing the glucose-insulin regulatory system that Ackerman proposed earlier.The enhanced approach may provide clinicians in endocrinology and metabolism field insight into the transition nature of human metabolic mechanism from normal to impaired glucose tolerance.展开更多
Glucagon-like peptide 1(GLP-1)is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors(GLP-1Rs)on pancreatic...Glucagon-like peptide 1(GLP-1)is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors(GLP-1Rs)on pancreaticβcells.Several GLP-1 mimetics,such as exenatide(exendin-4(Ex-4)),liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-展开更多
AIM: To investigate the incidence of reflux esophagitis (RE) and H pylori infection in the diabetic patient. METHODS: The incidence of RE and H pylori infection were investigated in 85 patients with diabetes mellitus ...AIM: To investigate the incidence of reflux esophagitis (RE) and H pylori infection in the diabetic patient. METHODS: The incidence of RE and H pylori infection were investigated in 85 patients with diabetes mellitus and the results were compared with controls. RESULTS: The incidence of RE in diabetic patients was 17.6%. Although this tended to be higher in diabetic patients, there were no statistically significant differences between diabetic patients and controls. The incidence of H pylori infection in diabetic patients was 53.7% but no statistically significant difference was seen between diabetic patients and controls in the incidence of H pylori infection. CONCLUSION: No significant differences could be seen between diabetic patients and controls in the incidence of RE and H pylori infection.展开更多
Objective: The objective is to assess the relationship of Log (TG)/HDL-c as surrogate estimate of atherogenic dyslipidemia with urinary albumin excretion rate and cardiovascular risk among black patients with type 2 d...Objective: The objective is to assess the relationship of Log (TG)/HDL-c as surrogate estimate of atherogenic dyslipidemia with urinary albumin excretion rate and cardiovascular risk among black patients with type 2 diabetes. Patients and methods: A post-hoc analysis of data from 181 type 2 diabetes patients enrolled in a cross-sectional study of urinary albumin excretion rate seen at a tertiary healthcare. Microalbuminuria and macroalbuminuria were defined as ACR 30 - 299.9 mg/g and ACR ≥ 300 mg/g, respectively. Quartiles of Log (TG)/HDL-c were used as surrogate estimates of atherogenic dyslipidemia. Cardiovascular risk was assessed using WHO chart for estimation of CV risk in low and middle income countries. Comparisons across Log (TG)/HDL-c quartiles were performed using one way ANOVA and Chi square for trend as appropriate. P < 0.05 defined the level of statistical significance. Results: A high prevalence (69%) of atherogenic dyslipidemia (AD) was observed in the present case series of Black Africans with type 2 diabetes. Average total cholesterol levels showed significant (p = 0.010) trends towards lower values across quartiles of Log (TG)/ HDL-c. No significant trends were observed for average UAER and cardiovascular risk across quartiles of Log (TG)/HDL-c. Conclusion: Log (TG)/HDL-c as a surrogate estimate of atherogenic failed to predict cardiovascular risk in the present case series of black patients with type 2 diabetes.展开更多
AIM: To investigate whether active glucagon-like peptide-1(GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus(GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with...AIM: To investigate whether active glucagon-like peptide-1(GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus(GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with type 2 diabetes, who had insufficient glycemic control [Hemoglobin A1c(Hb A1c) ≥ 7%] in spite of treatment with metformin and/or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin. RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of Hb A1c(7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of Hb A1c(7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months. Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significantexplanatory variable for an Hb A1 c decrease of ≥ 0.5%, and its odds ratio is 4.5(1.40-17.6)(P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for Hb A1 c level before administration, patients' medical history, medications, insulin secretion and insulin resistance.CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.展开更多
Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron...Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.展开更多
Glucagon-like peptide 1 (GLP-1) is a hormone, inducing glucose-dependent stimulation of insulin secretion from beta cells. Liraglutide acts as a GLP-1 receptor agonist. To assess the effect of liraglutide on the beta ...Glucagon-like peptide 1 (GLP-1) is a hormone, inducing glucose-dependent stimulation of insulin secretion from beta cells. Liraglutide acts as a GLP-1 receptor agonist. To assess the effect of liraglutide on the beta cell function, we performed oral glucose tolerance tests in 7 subjects with type 2 diabetes before and after treatment of liraglutide. Moreover, we performed same study again in 4 subjects at 6 months after induction. Liraglutide significantly increased area under the Curve (AUC) of plasma insulin level after glucose loading and significantly decreased AUC of plasma glucose level, compared with before induction. HOMA-beta was significantly increased, whereas insulinogenic index was not changed. HOMA-R was not affected but Matsuda index was significantly decreased after induction of liraglutide. Disposition index was not altered significantly, but tendency of improvement was observed. Glucose tolerance tests revealed that those effects of liraglutide were continued for 6 months after induction. These results showed that treatment of liraglutide could improve insulin secretion but early phase of insulin secretion was not improved. The results suggest that liraglutide is likely to improve beta-cell function, but this effect is still inadequate by six-month treatment.展开更多
基金Supported by Qatar Diabetic Association and Qatar National Research Fund, QNRF UREP 07-099-3-023
文摘AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.
文摘Atherosclerotic involvements are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis(CA) being a common risk-factor for prospective crisis of coronary artery diseases(CAD) and/or cerebral infarction(CI) in DM subjects. From another point of view, several reports have supplied augmenting proof that hepatocyte growth factor(HGF) has a physiopathological part in DM involvements. HGF has been a mesenchymal-derived polyphenic factor which modulates development, motion, and morphosis of diverse cells, and has been regarded as a humor intermediator of epithelial-mesenchymal interplays. The serum concentrations of HGF have been elevated in subjects with CAD and CI, especially during the acute phase of both disturbances. In our study with 89 type 2 DM patients, the association between serum concentrationsof HGF and risk-factors for macrovascular complicationsinclusive of CA were examined. The average of serumHGF levels in the subjects was more elevated than thereference interval. The serum HGF concentrations associated positively with both intimal-media thickness(IMT)(r = 0.24, P = 0.0248) and plaque score(r = 0.27, P =0.0126), indicating a relationship between the elevatedHGF concentrations and advancement of CA involvements. Multivariate statistical analysis accentuated thatserum concentrations of HGF would be associated inde-pendently with IMT(standardized = 0.28, P = 0.0499).The review indicates what is presently known regardingserum HGF might be a new and meaningful biomarkerof macroangiopathy in DM subjects.
文摘Progression of normal glucose tolerance(NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance(IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus(type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options(lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed.
文摘Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.
基金supported by National Institute on Aging RF1 AG061872 (to XH)NIH High Priority, Short-Term Project Award R56 AG061729 (to XH)National Institute on Aging RF1 AG061729 (to XH)
文摘Lipids play essential biological functions that include acting as components of biological membranes,energy storage,signaling,nutrients,transporters,enzyme activators,among others.Compared with the multiple research methods to assess DNA,RNA,and protein content,location,and function in cells,there are relatively fewer methods to study lipids.Therefore,lipid-oriented mechanistic studies remain rare and challenging.
文摘The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.
文摘AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence(1979-2008) and mortality(1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality(ASMR) and incidence(ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer(PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel(Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software(Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma(IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio(1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years(2018) relative to 2008, particularly as a result of IHBD. CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.
文摘Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.
文摘Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.
文摘AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 DM.Mean age was 64.7 years,mean body mass index was 24.7 RESULTS Lower abdominal symptoms were found to be more frequent than those affecting the upper abdomen.Diabetic duration and medications showed associations with GI symptoms.We identified differences in peak prevalences of the five symptoms.Gastralgia(P=0.02vs 10-14 years)and total GI symptoms(P=0.01 and P=0.02 vs 5-9 years and 10-14 years,respectively)peaked at a diabetes duration of 15-19 years.Heartburn(P=0.004)and postprandial fullness(P=0.03)tended to increase with disease duration.Constipation and diarrhea showed bimodal peaks,with the first early and the second late(e.g.,P=0.03 at 15-19 years vs 10-14years for diarrhea)in the disease course.Finally,GI symptoms showed clustering that reflected the region of the GI tract affected,i.e.,constipation and diarrhea had similar frequencies(P<0.0001). CONCLUSION Our study highlights the importance of questioning patients about QOL impairment due to abdominal symptoms,especially in the early and the late periods of diabetes.
文摘AIM:To investigate all patients referred to our center with non-responsive celiac disease (NRCD),to establish a cause for their continued symptoms.METHODS:We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period.These individuals were investigated to establish the eitiology of their continued symptoms.The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement.They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion.A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible.Colonoscopy,lactulose hydrogen breath testing,pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted.Their clinical progress was followed over a minimum of 2 years.RESULTS:One hundred and twelve consecutive patients were referred with NRCD.Twelve were found not to have celiac disease (CD).Of the remaining 100 patients,45% were not adequately adhering to a strict gluten-free diet,with 24 (53%) found to be inadvertently ingesting gluten,and 21 (47%) admitting noncompliance.Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%.Refractory CD was diagnosed in 9%.Three of these were diagnosed with intestinal lymphoma.After 2 years,78 patients remained well,eight had continuing symptoms,and four had died.CONCLUSION:In individuals with NRCD,a remediable cause can be found in 90%:with continued gluten ingestion as the leading cause.We propose an algorithm for investigation.
基金supported by a grant from the NIH(No.U42 RR16607)
文摘Objective:A computational model of insulin secretion and glucose metabolism for assisting the diagnosis of diabetes mellitus in clinical research is introduced.The proposed method for the estimation of parameters for a system of ordinary differential equations(ODEs)that represent the time course of plasma glucose and insulin concentrations during glucose tolerance test(GTT)in physiological studies is presented.The aim of this study was to explore how to interpret those laboratory glucose and insulin data as well as enhance the Ackerman mathematical model.Methods:Parameters estimation for a system of ODEs was performed by minimizing the sum of squared residuals(SSR)function,which quantifies the difference between theoretical model predictions and GTT's experimental observations.Our proposed perturbation search and multiple-shooting methods were applied during the estimating process.Results:Based on the Ackerman's published data,we estimated the key parameters by applying R-based iterative computer programs.As a result,the theoretically simulated curves perfectly matched the experimental data points.Our model showed that the estimated parameters,computed frequency and period values,were proven a good indicator of diabetes.Conclusion:The present paper introduces a computational algorithm to biomedical problems,particularly to endocrinology and metabolism fields,which involves two coupled differential equations with four parameters describing the glucose-insulin regulatory system that Ackerman proposed earlier.The enhanced approach may provide clinicians in endocrinology and metabolism field insight into the transition nature of human metabolic mechanism from normal to impaired glucose tolerance.
基金supported by a Grant-in-aid for Scientific Research from the Ministry of EducationScience+3 种基金Sports and Culture of Japan(grant number:25430056)the fund from Nukada Institute for Medical and Biological ResearchChibaJapan
文摘Glucagon-like peptide 1(GLP-1)is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors(GLP-1Rs)on pancreaticβcells.Several GLP-1 mimetics,such as exenatide(exendin-4(Ex-4)),liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-
文摘AIM: To investigate the incidence of reflux esophagitis (RE) and H pylori infection in the diabetic patient. METHODS: The incidence of RE and H pylori infection were investigated in 85 patients with diabetes mellitus and the results were compared with controls. RESULTS: The incidence of RE in diabetic patients was 17.6%. Although this tended to be higher in diabetic patients, there were no statistically significant differences between diabetic patients and controls. The incidence of H pylori infection in diabetic patients was 53.7% but no statistically significant difference was seen between diabetic patients and controls in the incidence of H pylori infection. CONCLUSION: No significant differences could be seen between diabetic patients and controls in the incidence of RE and H pylori infection.
文摘Objective: The objective is to assess the relationship of Log (TG)/HDL-c as surrogate estimate of atherogenic dyslipidemia with urinary albumin excretion rate and cardiovascular risk among black patients with type 2 diabetes. Patients and methods: A post-hoc analysis of data from 181 type 2 diabetes patients enrolled in a cross-sectional study of urinary albumin excretion rate seen at a tertiary healthcare. Microalbuminuria and macroalbuminuria were defined as ACR 30 - 299.9 mg/g and ACR ≥ 300 mg/g, respectively. Quartiles of Log (TG)/HDL-c were used as surrogate estimates of atherogenic dyslipidemia. Cardiovascular risk was assessed using WHO chart for estimation of CV risk in low and middle income countries. Comparisons across Log (TG)/HDL-c quartiles were performed using one way ANOVA and Chi square for trend as appropriate. P < 0.05 defined the level of statistical significance. Results: A high prevalence (69%) of atherogenic dyslipidemia (AD) was observed in the present case series of Black Africans with type 2 diabetes. Average total cholesterol levels showed significant (p = 0.010) trends towards lower values across quartiles of Log (TG)/ HDL-c. No significant trends were observed for average UAER and cardiovascular risk across quartiles of Log (TG)/HDL-c. Conclusion: Log (TG)/HDL-c as a surrogate estimate of atherogenic failed to predict cardiovascular risk in the present case series of black patients with type 2 diabetes.
文摘AIM: To investigate whether active glucagon-like peptide-1(GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus(GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with type 2 diabetes, who had insufficient glycemic control [Hemoglobin A1c(Hb A1c) ≥ 7%] in spite of treatment with metformin and/or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin. RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of Hb A1c(7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of Hb A1c(7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months. Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significantexplanatory variable for an Hb A1 c decrease of ≥ 0.5%, and its odds ratio is 4.5(1.40-17.6)(P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for Hb A1 c level before administration, patients' medical history, medications, insulin secretion and insulin resistance.CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.
基金Supported by Royal Golden Jubilee Ph D Program of Thailand Research Fund(Grant No.PHD/0345/2552)Faculty of Medicine Research Fund,Chiang Mai University,ThailandChair Professor Grant of National Science and Technology Development Agency through Professor Suthat Fucharoen,MD
文摘Objective:To evaluate the efficacy of deferiprone(DFP),1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)or green tea extract(GTE)in enhancing expression of hepatic hepcidin1(Hamp1)m RNA and relieving iron overload in b-globin knockout thalassemic mice.Methods:The b-globin knockout thalassemic mice were fed with a ferrocenesupplemented diet for 2 months and oral administration of deionized water,DFP(50 mg/kg),CM1(50 mg/kg),GTE(50 mg epigallocatechin 3-gallate equivalent/kg),GTE along with DFP(50 mg/kg),and GTE along with CM1(50 mg/kg)every day for 3months.Levels of hepatic Hamp1 m RNA,plasma non-transferrin bound iron,plasma alanine aminotransferase activity and tissue iron content were determined.Results:All chelation treatments could reduce plasma non-transferrin bound iron concentrations.Additionally,hepatic Hamp1 m RNA expression was significantly upregulated in the mice in a GTE+DFP combined treatment,correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition.Conclusions:The GTE+DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent b-thalassemic mice,by chelating toxic iron in plasma and tissues,and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen.There is probably an advantage in giving GTE with DFP when treating patients with iron overload.
文摘Glucagon-like peptide 1 (GLP-1) is a hormone, inducing glucose-dependent stimulation of insulin secretion from beta cells. Liraglutide acts as a GLP-1 receptor agonist. To assess the effect of liraglutide on the beta cell function, we performed oral glucose tolerance tests in 7 subjects with type 2 diabetes before and after treatment of liraglutide. Moreover, we performed same study again in 4 subjects at 6 months after induction. Liraglutide significantly increased area under the Curve (AUC) of plasma insulin level after glucose loading and significantly decreased AUC of plasma glucose level, compared with before induction. HOMA-beta was significantly increased, whereas insulinogenic index was not changed. HOMA-R was not affected but Matsuda index was significantly decreased after induction of liraglutide. Disposition index was not altered significantly, but tendency of improvement was observed. Glucose tolerance tests revealed that those effects of liraglutide were continued for 6 months after induction. These results showed that treatment of liraglutide could improve insulin secretion but early phase of insulin secretion was not improved. The results suggest that liraglutide is likely to improve beta-cell function, but this effect is still inadequate by six-month treatment.
