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PubMed2006

Ala45Thr variation in neuroD1 gene is associated with early-onset type 2 diabetes with or without diabetic pedigree in Chinese.

OBJECTIVE: Based on onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous type 2 diabetes mellitus (T2DM), we investigated the Ala45Thr variation in unrelated early-onset and late-onset T2DM with or without diabetic pedigree and unrelated non-diabetic control subjects in Chinese. METHODS: 175 early-onset and 194 late-onset type 2 diabetic patients were further divided into two subgroups according to with or without diabetic pedigree respectively. This NeuroD1-Ala45Thr variation were screened by PCR-direct sequencing in above 369 type 2 diabetic patients and 87 unrelated non-diabetic control subjects. We then compared the distribution of the Ala45Thr variation among the groups, searching for the predictive trends. RESULTS: Frequencies of the variant (AA + GA genotype) in early-onset T2DM are obviously elevated, especially among diabetic pedigree subjects when compared to non-diabetic controls (p= 0.003) and late-onset T2DM subjects (p = 0.014). However, no significant differences were observed between late-onset T2DM with or without diabetic pedigree and non-diabetic control subjects. CONCLUSIONS: Our results suggest that 1) the NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese; 2) the Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese; and 3) onset-age stratified analysis may be useful to determine the association of NeuroD1-Ala45Thr variation with susceptibility to genetic heterogeneous T2DM in Chinese.

Adult↗

PubMed2006

The effect of the ingestion of Ginkgo biloba extract (EGb 761) on the pharmacokinetics of metformin in non-diabetic and type 2 diabetic subjects--a double blind placebo-controlled, crossover study.

BACKGROUND & AIMS: Ginkgo biloba extract (EGb 761) has been shown to ameliorate some defects associated with the insulin resistance syndrome and so patients with Type 2 diabetes mellitus (T2DM) may be inclined to co-ingest the herb with their medications, such as metformin. This study was designed to determine if the co-ingestion of EGb 761 and metformin would alter the pharmacokinetic properties of metformin in T2DM patients and persons without diabetes, who may ingest it for other purposes. METHOD: Normal glucose tolerance (NGT) subjects (n=10; age, 39.2+/-14.0 years; fasting plasma glucose (FPG), 90+/-7 mg/dl; body mass index (BMI), 24.1+/-3.7 kg/m(2)) and 10 T2DM patients (n=10; age, 51.7+/-8.9 years; FPG, 150+/-7 mg/dl; BMI, 33.7+/-5.7 kg/m(2)) completed a randomized, double-blind, placebo-controlled crossover study. They ingested either EGb 761 (12 0mg/day as a single dose) or a vegetable-based placebo during each arm for 3 months. At the end of each arm, the NGT subject ingested a single 500 mg dose of metformin (non-diabetics) and the T2DM subject took his/her prescribed metformin dose (250-850 mg) with 120 mg EGb 761. Blood and urine samples were collected over an 8-h period, and in the case of T2DM subjects, additionally over the first 2h of the subsequent 3 days. RESULTS: Ingestion of EGb 761 produced no significant changes in diagnostic laboratory tests in either group, except reducing glycosylated hemoglobin A(1c) levels (from 7.7+/-1.2 to 7.2+/-0.9%, P<0.05) in T2DM the subjects. The pharmacokinetic parameters of metformin were all significantly different (P<0.05) between the NGT (500 mg) and 8 out of 10 of the T2DM subjects who were prescribed 500 mg of metformin during the placebo cycles. During the EGb 761 cycles, only the elimination half-life in the T2DM subjects was significantly increased (0.117+/-0.085 to 0.141+/-0.100, P<0.05). CONCLUSION: The co-ingestion of 120 mg of EGb 761 and 500 mg of metformin did not significantly affect the pharmacokinetic properties of metformin. Further studies are required to verify this observation for smaller and larger dose of metformin with other doses of EGb 761, since T2DM patients on medication constitute a very heterogeneous group.

Adult↗

PubMed2005

Is Roux-en-Y gastric bypass surgery the most effective treatment for type 2 diabetes mellitus in morbidly obese patients?

Type 2 diabetes mellitus (T2DM) has a very strong association with obesity. The aim of our study was to analyze the effects of Roux-en-Y gastric bypass (RYGB) surgery on the glucose metabolism in morbidly obese patients with T2DM. Morbidly obese patients (n = 117) with T2DM underwent measurements of fasting serum glucose and glycosylated hemoglobin (HbA1C) at baseline, 6 months, and 12 months after laparoscopic RYGB surgery. Logistic regression was used in both univariate and multivariate modeling to identify independent variables associated with complete resolution of T2DM. Twelve months after surgery, fasting plasma glucose decreased from a preoperative mean of 164 +/- 55 mg/dL to 101 +/- 38 mg/dL (P = .001) and HbA1C decreased from a preoperative mean of 7.7% +/- 1.5% to 6.0% +/- 1.1% (P = .001). Resolution of T2DM was achieved in 72 patients (74%). All of the remaining 25 patients decreased the daily medication requirements. On univariate analysis, preoperative variables associated with resolution of T2DM were waist circumference, HbA1C, and absence of insulin treatment. Waist circumference (odds ratio 2.4; 95% confidence interval 1.4-4.1; P = .001) and treatment without insulin (odds ratio 42.2; 95% confidence interval 4.3-417.3; P = .002) remained significant predictors of T2DM resolution in the multivariate logistic regression model after adjusting for covariates. Laparoscopic RYGBP resulted in significant resolution of T2DM. Peripheral fat distribution (smaller waist circumference) and absence of insulin treatment were independent and significant predictors of complete resolution of T2DM.

Adult↗

PubMed2006

Myocardial glucose transport and utilization in patients with type 2 diabetes mellitus, left ventricular dysfunction, and coronary artery disease.

OBJECTIVES: This research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease. BACKGROUND: Patients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose. METHODS: Myocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by 18F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts. RESULTS: Myocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 +/- 0.16 vs. 0.47 +/- 0.24 micromol x min(-1) x g(-1), p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 +/- 3.1% vs. 13.5 +/- 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75). CONCLUSIONS: Patients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients.

Aged↗

PubMed2006

Noncompliance with vision care guidelines in Latinos with type 2 diabetes mellitus: the Los Angeles Latino Eye Study.

OBJECTIVE: To determine the prevalence of and personal factors associated with noncompliance with American Diabetes Association (ADA) guidelines for vision care in a population-based sample of adult Latinos with type 2 diabetes mellitus (T2DM). DESIGN: Population-based cross-sectional study. PARTICIPANTS: Eight hundred twenty-one Los Angeles Latino Eye Study (LALES) participants with a history of T2DM and a history of treatment for T2DM. METHODS: Detailed interviews, physical examinations, and dilated eye examinations were performed on all participants. Interviews assessed sociodemographic factors, history of diabetes and eye disease, and utilization of health and eye care services. All participants with a self-reported history and treatment of diabetes were asked about health and vision care utilization and diabetes self-care. MAIN OUTCOME MEASURE: Compliance with ADA guidelines for vision care. Noncompliance was defined as having had no dilated eye examination in the previous 12 months. Logistic regression analyses were used to identify personal factors associated with noncompliance. RESULTS: Of 821 individuals who self-reported having T2DM and being on treatment for T2DM, 535 (65%) had not complied with ADA vision guidelines for persons with T2DM. When compared with those with T2DM who complied with ADA guidelines, noncompliers were more likely to be less educated (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.2), to lack health insurance (OR, 2.5; 95% CI, 1.7-3.7), to have had no routine physical examination in the 12 months before the LALES examination (OR, 1.8; 95% CI, 1.3-2.5), and to have a glycosylated hemoglobin level > or = 9.0% (OR, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: Because timely and appropriate vision care can delay the onset of ocular morbidity, visual impairment, and blindness associated with diabetic retinopathy, our data suggest the need to evaluate intervention programs aimed at a targeted group of Latinos with T2DM--those who have less than a high school education, lack health insurance, have had no routine physical examination in the previous year, and have poorly controlled T2DM.

Aged↗

PubMed2003

The Pro12Ala polymorphism of PPARgamma2 gene and susceptibility to type 2 diabetes mellitus in a Polish population.

INTRODUCTION: It has recently been shown that polymorphisms of some genes might influence the genetic susceptibility to complex, multifactorial forms of type 2 diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated receptor gamma (PPARgamma). The PPARgamma gene product is a nuclear hormone receptor that regulates adipogenesis and is a target for thiazolidinediones, medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of the PPARgamma2 isoform is associated with T2DM in several populations. AIMS: (1) To determine the allele and genotype frequency of the Pro12Ala PPARgamma2 amino acid variant in a Polish population; (2) To search for the association of the Pro12Ala polymorphism with T2DM in the examined population. METHODS: We included 644 individuals in this study: 366 T2DM patients with age of diagnosis greater than 35 years and 278 non-diabetic control subjects. The fragment of the PPARgamma2 gene which contains the examined amino acid variant was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by the specific restriction enzyme BshI. Differences in distribution between the groups were examined by chi2 test. RESULTS: The frequency of Pro/Ala alleles was similar in T2DM patients and in the control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P=0.607). Similarly, there was no difference between the groups when we analysed the genotype distribution. Stratification analyses based on age of diagnosis, body mass index (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala genotypes tended to be more frequent in T2DM cases with age of diagnosis >50 years than in controls (36.2% vs. 27.3%, P=0.046). This difference was not significant after Sheffe correction for multiple comparisons. The other stratification analyses did not show any difference between the groups. CONCLUSION: The frequency of the Pro12Ala PPARgamma2 polymorphism in the Polish population studied is similar to that in other Caucasian populations. In the case-control study, we were not able to confirm earlier reports that the Pro allele conferred an increased risk for development of T2DM. Moreover, the results of the stratified analysis suggest an opposite trend in late onset T2DM.

Age of Onset↗

PubMed2003

Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.

OBJECTIVE: To evaluate pre- and postoperative clinical parameters associated with improvement of diabetes up to 4 years after laparoscopic Roux-en-Y gastric bypass (LRYGBP) in patients with type 2 diabetes mellitus (T2DM). SUMMARY BACKGROUND DATA: The surgical treatment of morbid obesity leads to dramatic improvement in the comorbidity status of most patients with T2DM. However, little is known concerning what preoperative clinical factors are associated with postoperative long-term improvement in diabetes in the morbidly obese patient with diabetes. METHODS We evaluated pre- and postoperative data, including demographics, duration of diabetes, metabolic parameters, and clinical outcomes, in all patients with impaired fasting glucose (IFG) and type T2DM undergoing LRYGBP from July 1997 to May 2002. RESULTS: During this 5-year period, 1160 patients underwent LRYGBP and 240 (21%) had IFG or T2DM. Follow up was possible in 191 of 240 patients (80%). There were 144 females (75%) with a mean preoperative age of 48 years (range, 26-67 years). After surgery, weight and body mass index decreased from 308 lbs and 50.1 kg/m2 to 211 lbs and 34 kg/m2 for a mean weight loss of 97 lbs and mean excess weight loss of 60%. Fasting plasma glucose and glycosylated hemoglobin concentrations returned to normal levels (83%) or markedly improved (17%) in all patients. A significant reduction in use of oral antidiabetic agents (80%) and insulin (79%) followed surgical treatment. Patients with the shortest duration (<5 years), the mildest form of T2DM (diet controlled), and the greatest weight loss after surgery were most likely to achieve complete resolution of T2DM. CONCLUSION: LRYGBP resulted in significant weight loss (60% percent of excess body weight loss) and resolution (83%) of T2DM. Patients with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery, suggesting that early surgical intervention is warranted to increase the likelihood of rendering patients euglycemic.

Adult↗

PubMed2006

Putative association of peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B) polymorphism with Type 2 diabetes mellitus.

AIMS: Peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B) may play an important role in obesity and Type 2 diabetes mellitus (T2DM). In an effort to identify genetic polymorphisms in potential candidate genes for T2DM, genetic associations of PPARGC1B were examined in a Korean T2DM study. METHODS: We have sequenced the PPARGC1B, and examined its association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 control subjects) using the TaqMan method. Logistic and multiple regression models were employed to analyse the genetic contributions of polymorphisms. Nineteen polymorphisms were identified in PPARGC1B. RESULTS: By logistic regression analysis controlling for age and sex as covariates, one non-synonymous single-nucleotide polymorphism (SNP; +102605C>A; Arg292Ser) in exon 5 showed marginal significant associations with the risk of T2DM. The allele frequency of the minor allele ['A (= Ser)' allele of +102605C>A] was lower among T2DM patients (frequency = 0.101) than among control subjects (frequency = 0.135) [P = 0.03, OR = 0.71 (95% CI: 0.51-0.94)]. Furthermore, serum triglyceride level was also associated with this non-synonymous SNP (+102605C>A; Arg292Ser) in exon 5 among controls (P = 0.03 in the dominant analysing model). Serum triglyceride levels [1.46 +/- 0.70 (log-transformed value; 0.12 +/- 0.18)] were lower in individuals who carry one or two copies of minor alleles than among others [1.60 +/- 0.85 (log-transformed value; 0.16 +/- 0.21)]. CONCLUSION: The present study provides, for the first time, information about genetic polymorphisms in PPARGC1B and putative associations of one non-synonymous SNP with the risk of T2DM and serum triglyceride (TG) levels in the Korean population, although this result was not significant after correction for multiple testing.

Asian People↗

PubMed2003

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes.

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P < 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P < 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P < 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P < 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.

Adiponectin↗

PubMed2005

Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes.

BACKGROUND: GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans. METHODS: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM. RESULTS: Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P > or = 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls. CONCLUSION: From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.

Adult↗

PubMed2004

Epitope-restricted 65-kilodalton glutamic acid decarboxylase autoantibodies among new-onset Sardinian type 2 diabetes patients define phenotypes of autoimmune diabetes.

The 65-kDa glutamic acid decarboxylase (GAD65) autoantibodies (GAD65Abs), commonly found in type 1 diabetes mellitus (T1DM) patients, are also found at lower frequencies in type 2 diabetes mellitus (T2DM) patients. GAD65Abs in T1DM patients are epitope specific, in contrast to those found in other GAD65Ab-positive individuals, including T2DM patients. Our aim was to assess whether epitope-specific GAD65Abs, or the additional presence of islet antigen 2 (IA-2) autoantibodies, better define T1DM phenotypes among T2DM patients. GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. Autoantibody binding specificity to the N-terminal, middle (M), and C-terminal (C) portions of the GAD65 molecule was evaluated. Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. GAD65Ab-positive T2DM patients with M+C (epitope-specific) reactivity were found to have the lowest body mass index (P < 0.001), followed by GAD65Ab/IA-2Ab-positive patients (P < 0.01), and non-M+C-reactive (non-epitope-specific) patients (P < 0.02). In GAD65Ab-positive T2DM patients, c-peptide levels were lower in M+C-reactive compared with non-M+C-reactive patients. Sardinian T2DM patients with M+C-predominant GAD65Ab reactivity have clinical features more similar to those of T1DM patients. Thus, GAD65Ab epitope analysis may help to define T1DM phenotypes among newly diagnosed GAD65Ab-positive patients classified with T2DM.

Adult↗

PubMed2006

[Detecting of mtDNA mutations at position A3243G and G3316A in patients with type 2 diabetes mellitus in Wenzhou].

To investigate the frequencies of mitochondria DNA (mtDNA) tRNA(Leu (UUR)) point mutation A3243G and NADH dehydronase subunit 1(ND1) gene point mutation G3316A in Wenzhou area of Zhejiang Province, and to explore the correlation between these mutations and the clinical manifestations in patients with type 2 mellitus diabetes(T2DM). Two hundreds and forty-four unrelated patients with T2DM and 156 healthy subjects without family history of T2DM were enrolled in Wenzhou area in this study and screened for the point mutations mentioned above with polymerase chain reaction (PCR) and restricted fragment length polymorphism(RFLP) analysis. The heterogeneous mutations were confirmed with DNA sequencing and denaturing high performance liquid chromatography (DHPLC) following T-A cloning of PCR products. The percentage of A3243G mutation in group of patients with T2DM and control were 0.410% and 0.0% (1/244 vs 0/156), respectively; however, there's not any significant difference between these two groups in frequency of A3243G mutation (P>0.05). G3316A mutation was detected in 4 of 244 cases with T2DM (1.639%) and 2 of 156 healthy controls (1.282%), showing that there's also no statistic difference between these two groups in frequency of G3316A mutation (P>0.05). It's shown that the frequency of mtDNA tRNA(Leu (UUR)) A3243G mutation is fairly low in patients with T2DM in Wenzhou area. Thus it's reasonable to assume that this mutation may not be involved in the development and progression of T2DM. Furthermore, it's demonstrated that the rate of G3316A mutation of mtDNA ND1 gene is rare in patients with T2DM in Wenzhou area and this mutation also happened in healthy control. It's suggested that G3316A mutation is just a gene polymorphism of mtDNA and not related to the pathogenesis of T2DM.

Asian People↗

PubMed2025

Network pharmacology-based study on the mechanism of Tangfukang formula against type 2 diabetes mellitus.

OBJECTIVE: To explore the mechanism of Tangfukang formula (, TFK) in treating type 2 diabetes mellitus (T2DM). METHODS: We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM. Initially, we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Symptom Mapping (SymMap), and gathered targets of TFK and T2DM. Subsequently, we constructed a protein-protein interaction (PPI) network, enriched core targets through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and adopted molecular docking to study the binding mode of compounds and the signaling pathway. Finally, we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM. Biochemical assay, histology assay, and Western blot (WB) were used to assess the mechanism. RESULTS: There were 492 bioactive compounds of TFK screened, and 1226 overlapping targets of TFK against T2DM identified. A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed. KEGG enrichment analysis identified some core pathways related to T2DM, including adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway. Molecular docking study revealed that compounds of TFK, including citric acid, could bind to the active pocket of AMPK crystal structure with free binding energy of －4.8, －8 and －7.9, respectively. Animal experiments indicated that TFK decreased body weight, fasting blood glucose, fasting serum insulin, homeostasis model of insulin resistance, glycosylated serum protein, total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and improve oral glucose tolerance test results. TFK reduced steatosis in liver tissue, and infiltration of inflammatory cells, and protected liver cells to a certain extent. WB analysis revealed that, TFK upregulated the phosphorylation of AMPK and branched-chain α-ketoacid dehydrogenase proteins. CONCLUSION: TFK has the potential to effectively manage T2DM, possibly by regulating the AMPK signaling pathway. The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.

Diabetes Mellitus, Type 2↗

PubMedDate not supplied

[The prevalence of hypertension and microalbuminuria in diabetes mellitus type 1 and type 2].

INTRODUCTION: The prevalence of hypertension is two times higher in diabetics than in non-diabetics. In type 1 diabetes mellitus (T1DM), the incidence of hypertension is similar to the incidence of nephropathy. In obese patients with type 2 DM (T2DM) there can be associated complications of hyperinsulinaemia, dyslipidaemia, and hypertension, which can lead to coronary artery disease and stroke. These associated complications are the result of a genetic defect that produces insulin resistance--Syndrome X. Increased microalbuminuria correlates with increased levels of blood pressure (BP) and increased LDL cholesterol, and this is why microalbuminuria is associated with an increase in cardiovascular deaths in diabetics, even in the absence of renal failure. AIM: The aim of this study was to research the influence of a patient's age, diabetes duration, and obesity on the frequency of hypertension and its association with microalbuminuria in T1 DM and T2DM. METHOD: 168 hospitalised patients with DM (79 T1DM, 89 T2DM) were analysed. The main outcome measures were: 24-hour urinary albumin excretion rate by radioimmunoassay (MA = 30-300 mg/24h), arterial hypertension (systolic BP > or = 140 mm Hg and/or diastolic BP > or = 90 mm Hg), and body mass index (BMI). RESULTS: Microalbuminuria was detected in 42% of patients with T1DM and 47% of patients with T2DM. 34% of T1DM patients and 78% of T2DM patients were hypertensive. Patients were divided into four groups, according to the presence of hypertension and microalbuminuria: Group I--patients with hypertension and MA, Group II--patients with hypertension but without MA, Group III--patients without hypertension and MA, Group IV--patients without hypertension but with MA. 44% of T1DM patients were without hypertension and microalbuminuria, while the most frequent T2DM patients were those with hypertension (37% with and 41% without microalbuminuria). A significant correlation between BMI and diastolic BP in both types of DM (p < 0.01 for T1DM, and p < 0.05 for T2DM) was discovered. T2DM hypertensive patients were obese and there was a significant correlation between a patient's systolic BP and his or her age (p < 0.05). CONCLUSION: These results suggest that hypertension can be prevented in patients with T2DM with weight reduction. There was a significant association between hypertension and microalbuminuria, especially in T1DM patients. Tight control of blood pressure is essential for the reduction of microalbuminuria as well as further micro- and macro-vascular diabetic complications.

Adult↗

PubMed2005

Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management.

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2002

Is type 2 diabetes a chronic inflammatory/autoimmune disease?

The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients diagnosed as having T2DM and most likely delay the onset of insulin requirement and the complications related with hyperglycemia.

Acute-Phase Reaction↗

PubMed2003

A search for association between hereditary hemochromatosis HFE gene mutations and type 2 diabetes mellitus in a Polish population.

BACKGROUND: Hereditary hemochromatosis (HH) is characterized by excess iron deposition. Two mutations in the HFE gene are associated with HH. Heterozygous carriers of HFE mutations are at higher risk of developing type 2 diabetes mellitus (T2DM). The aims of our project were to identify the frequency of C282Y and H63D mutations in a population from the Małopolska region of south-eastern Poland, and to search for an association of HFE mutations with T2DM. MATERIAL/METHODS: We included 391 individuals in this study: 222 T2DM patients and 169 controls. Genotypes were determined by electrophoresis of the DNA digestion products from SnaBI and DpnII, respectively. Differences in distributions between the groups were then analyzed by the chi-squared test. RESULTS: The frequency of wild/C282Y alleles was 98.2%/1.8% in T2DM patients and 96.7%/3.2% in controls (p=0.19). The frequency of wild/H63D alleles was 85.6%/14.4% and 88.8%/11.2% (p= 0.19), respectively. The distribution of genotypes was not statistically different. However, in stratified analyses based on age of T2DM onset and gender, we observed a higher prevalence of wild/H63D and H63D/H63D genotypes among T2DM patients diagnosed at > 49 years of age, the mean age for the entire group (p=0.018), and among male T2DM individuals (p=0.005) than in controls. CONCLUSIONS: The frequency of HH-associated mutations in this population from south-eastern Poland is similar to other Caucasians. We found no evidence for the association of the C282Y mutation with T2DM. The results do suggest, however, that the H63D mutation may play a role in the pathogenesis of late onset T2DM and in males in this Polish population.

Adult↗

PubMedDate not supplied

Metabolic disorders in children and adolescents with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) in children and adolescents is increasing in incidence worldwide. It is the leading type of newly diagnosed diabetes in Taiwan among school children. T2DM is associated with metabolic syndrome in adults, so we tried to find out if these metabolic disorders are present in children. METHODS: From 1989 to 2003, 22 children and adolescents were diagnosed with T2DM in our hospital. Their ages ranged from 8.8 to 17.0 (11.7+/-2.3) years; 6 of them were boys. We compared their clinical characteristics with those of 42 healthy and 237 obese children and adolescents. Physical examination was performed and plasma glucose and serum cholesterol, triglycerides, uric acid, creatinine, HDL-cholesterol, and insulin levels were measured and LDL-cholesterol was calculated. Demographic and laboratory data were compared among the T2DM, obese and control groups. RESULTS: The female: male ratio among the patients was 2.7: 1; 18% were overweight and 68% obese, and 64% had acanthosis nigricans. There were no significant differences between the T2DM and obese groups in terms of biochemistry profiles except for the higher plasma glucose in the T2DM group. Children with T2DM had higher levels of cholesterol and triglycerides but lower levels of HDL-cholesterol compared with healthy children. Among obese children without T2DM, the levels of glucose, triglycerides, uric acid, insulin, HOMA-IR were higher than in the healthy group, and HDL-cholesterol levels were lower. CONCLUSIONS: Children with T2DM or obesity should be evaluated for metabolic disorders.

Acanthosis Nigricans↗