SEARCH · Search PubMed

Results for “T2DM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗

PubMedDate not supplied

Rosiglitazone: safety and efficacy in combination with insulin in poorly controlled type 2 diabetes mellitus patients treated with insulin alone.

AIMS: To assess the safety and efficacy of rosiglitazone and insulin treatment in combination in poorly controlled insulin-treated type 2 diabetes mellitus (T2DM) patient. METHOD: In this prospective, open-labelled, nonrandomised study, rosiglitazone was added to the insulin therapy in T2DM patients with baseline HbA1c>or=7.5%. Patients were followed for 12 months. Insulin dosage was adjusted as necessary. RESULTS: Insulin and rosiglitazone combination was used in 53 patients (29 male, 24 female) for 12 months. Baseline vs. 12-month results shown as mean+/-S.D.: HbA1c reduction 1.53% (9.82+/-1.12 vs. 8.29+/-1.45, P=.0001), insulin dosage reduction 10 U (74+/-34 vs. 64+/-34 U), percentage insulin dose reduction 13.53%, and weight gain 1.0 kg only (84+/-19.93 vs. 85+/-25.73 kg, P=.1). Systolic blood pressure 144+/-22.9 vs. 134+/-15.8 mm Hg (P=.03), total cholesterol 6.18+/-4.15 vs. 4.75+/-2.71 micromol/L, triglyceride 2.62+/-1.49 vs. 2.07+/-1.44 micromol/L, and HDL cholesterol 1.43+/-0.71 vs. 1.63+/-0.36 micromol/L (P=.02). Alanine transaminase actually reduced significantly from 26+/-22 to 19+/-9 IU/L (P=.001). Improved glycaemic control was associated with favourable reduction in cardiovascular risk factors. Rosiglitazone was discontinued only in nine patients (weight gain-4, no improvement noticed-4, ankle swelling-1). No hepatotoxicity was observed. CONCLUSION: Rosiglitazone+insulin combination is safe and effective in inadequately controlled insulin-treated T2DM patients.

Aged↗

PubMed2004

Progressive beta cell failure in type 2 diabetes mellitus of youth.

The pathophysiology of type 2 diabetes mellitus (T2DM) involves insulin resistance and insulin deficiency. We report the progression in insulin sensitivity and secretion over a 6-year period in an adolescent with T2DM. This report further demonstrates that the earliest abnormality in youth T2DM is insulin resistance followed by progressive beta-cell failure.

Child↗

PubMed2004

DNA damage and repair in type 2 diabetes mellitus.

DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its complications mainly through oxidative stress. Little is known about DNA repair disturbances potentially contributing to the overall extent of DNA damage in T2DM, which, in turn, may be linked with genomic instability resulting in cancer. To assess whether DNA repair may be perturbed in 2DM we determined: (1) the level of endogenous basal DNA damage, this means damage recognized in the alkaline comet assay (DNA strand breaks and alkali labile sites) as well as endogenous oxidative and alkylative DNA damage (2) the sensitivity to DNA-damaging agents hydrogen peroxide and doxorubicin and the efficacy of removing of DNA damage induced by these agents in peripheral blood lymphocytes of T2DM patients and healthy individuals. The level of DNA damage and the kinetics of DNA repair was evaluated by the alkaline single cell gel electrophoresis (comet assay). Oxidative and alkylative DNA damage were assayed with the use of DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II (AlkA) recognizing alkylated bases. The levels of basal endogenous and oxidative DNA damage in diabetes patients were higher than in control subjects. There was no difference between the level of alkylative DNA in the patients and the controls. Diabetes patients displayed higher susceptibility to hydrogen peroxide and doxorubicin and decreased efficacy of repairing DNA damage induced by these agents than healthy controls. Our results suggest that type 2 diabetes mellitus may be associated not only with the elevated level of oxidative DNA damage but also with the increased susceptibility to mutagens and the decreased efficacy of DNA repair. These features may contribute to a link between diabetes and cancer and metrics of DNA damage and repair, measured by the comet assay, may be markers of risk of cancer in diabetes.

Aged↗

PubMed2004

C-reactive protein in young individuals: problems and implications for Asian Indians.

Recent data in adults showed that C-reactive protein (CRP) level robustly predicts future coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). Although data in children are scarce, overweight, obesity, and insulin resistance were shown to be associated with elevated CRP concentrations. Preliminary data in children also show association of CRP with endothelial dysfunction and other cardiovascular risk factors. Adult Asian Indians, highly predisposed to develop CHD and T2DM, have significantly higher CRP levels than do Europeans. Recent studies show that nearly 13% of Asian Indian children and young adults in India have subclinical inflammation, and approximately 20% have insulin resistance, portending high risk for CHD in adulthood. Possible determinants of high CRP levels in Asian Indians might be excess body fat, including high subcutaneous fat, and physical inactivity. The relationships of recurrent infections, protein deficiency, and subclinical inflammation in Asian Indians remain uninvestigated. Finally, prevention of childhood adiposity is critical to decrease future risk for development of T2DM and CHD, particularly in highly predisposed ethnic groups such as Asian Indians and South Asians.

Adolescent↗

PubMed2026

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide®) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N = 663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide®. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide® significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p < 0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p < 0.001). The direct effect on AQoL-6D was non-significant (p = 0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n = 563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p = 0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans↗

PubMed2004

The transcribed endosulfine alpha gene is located within a type 2 diabetes-linked region on 1q: sequence and expression analysis in Pima Indians.

Endosulfine alpha (ENSA) is an endogenous ligand of the sulfonylurea receptor 1 (SUR1) that can stimulate insulin secretion by pancreatic beta cells. Originally, an intronless gene coding for this protein was assigned to Chr. 14q, but more recent information available in public databases indicated the position of ENSA on 1q21. We show here that the 1q21 locus represents the expressed gene consisting of 6 exons, whereas the locus on Chr. 14q is apparently a pseudogene. The ENSA gene on 1q21 produces several alternatively spliced transcripts, and is located within a region linked with T2DM in diverse populations including the Pima Indians. We analyzed ENSA in this Native American population and identified seven variants, which fall into three linkage disequilibrium groups. Analysis of representative markers in over 1200 Pima Indians did not reveal any significant association with T2DM, or with differences in insulin action and insulin secretion in a subset of approximately 270 non-diabetic subjects. In addition, we did not detect any significant correlation of skeletal muscle ENSA transcript levels with differences in insulin action in 49 non-diabetic subjects. We conclude that sequence alterations in ENSA are an unlikely cause for the linkage of T2DM with 1q21-q23 in the Pima Indians.

Base Sequence↗

PubMed2002

Pathogenesis of feline diabetes mellitus.

The common form of spontaneous diabetes mellitus that occurs in domestic cats bears close resemblance clinically and pathologically to human type 2 diabetes mellitus (T2DM). For example, the typical diabetic cat is obese and middle-aged, and has low but detectable circulating insulin levels. However, the most striking similarity is the occurrence of islet amyloidosis (IA) in nearly all diabetic cats and in over 90% of humans with T2DM. IA in both humans and cats is derived from islet amyloid polypeptide (IAPP, or amylin) which is a hormone produced and secreted along with insulin by the pancreatic beta cells. Since all cats and humans normally produce IAPP, additional factors must be invoked in order to explain the development of IA. Several lines of evidence support the concept that IA is caused by chronically increased stimulus for beta cells to secrete IAPP (and insulin). For example, peripheral insulin resistance such as in chronic obesity results in increased IAPP and insulin secretion. A recent study, in which diabetes mellitus was induced in cats, demonstrated that IAPP hypersecretion was induced by treatment with a sulfonylurea drug and resulted in 4/4 cats in this group developing IA. In contrast, cats treated with insulin had low IAPP secretion and minimal IA developed in 1/4 cats. Several human-IAPP transgenic mouse models, in which there is IAPP overexpression, also support the notion that prolonged high expression of IAPP leads to IA. In vitro models of IAPP overexpression also support this mechanism for IA formation and by demonstrating an association between IA formation and beta cell toxicity, suggest a linkage between IA formation and loss of beta cells in T2DM. A recent study has indicated that intermediate-sized IAPP-derived amyloid fibrils can disrupt cell membranes and therefore, may be involved in the destruction of beta cells. Striking parallels between the pathogenesis of IA and beta-amyloid plaque formation in Alzheimer's disease suggest possible parallel pathogenetic mechanisms of cell death and provide potential avenues for future studies into the pathogenesis of IA.

Amyloid↗

PubMedDate not supplied

Starting patients with type 2 diabetes on insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin.

Transitioning safely to insulin therapy when oral antidiabetic agents fail to provide adequate glycemic control is a critical aspect of care for the patient with type 2 diabetes mellitus (T2DM). We evaluated the clinical effectiveness of starting patients on a relatively simple regimen of once-daily injections of either biphasic insulin aspart 70/30 (10 min before dinner), NPH insulin (at 10 p.m.), or biphasic human insulin 70/30 (30 min before dinner) in combination with metformin. Enrolled patients had T2DM and inadequate glycemic control (AlC>/=7.5%) on a previous regimen of metformin as monotherapy or in combination with a sulphonylurea. One hundred and forty (140) patients received metformin monotherapy for 4 weeks followed by 12 weeks of combination treatment with metformin and once-daily insulin injections. AlC levels decreased from baseline by 1.1-1.3% for patients in each of the three treatment groups. Overall, FPG values decreased from baseline by 31% (biphasic insulin aspart), 37% (NPH insulin), and 28% (biphasic human insulin). Subjects whose final FPG level was <126 mg/dl experienced the largest decreases in AlC values (-2.3%, -1.9%, -1.8%, respectively). All three treatment regimens were well tolerated. The results indicate that patients with T2DM can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin.

Administration, Oral↗

PubMedDate not supplied

Analysis of MGEA5 on 10q24.1-q24.3 encoding the beta-O-linked N-acetylglucosaminidase as a candidate gene for type 2 diabetes mellitus in Pima Indians.

Several diseases including type 2 diabetes mellitus (T2DM) are associated with abnormal O-glycosylation of proteins. beta-O-linked N-acetylglucosaminidase (O-GlcNAcase) encoded by MGEA5 on 10g24.1-q24.3 removes N-acetylglucosamine (O-GlcNAc), and we investigated this locus in Pima Indians who have the world's highest prevalence of T2DM. We detected two variants but there was no association with parameters of insulin resistance or diabetes in approximately 1300 Pimas. We conclude that mutations in MGEA5 are unlikely to contribute to T2DM in this population.

Acetylglucosaminidase↗

PubMed2003

Co-inheritance of specific genotypes of HSPG and ApoE gene increases risk of type 2 diabetic nephropathy.

The objective of this paper is to investigate co-inheritance of specific HSPG and ApoE genotypes in the development of Chinese type 2 diabetic nephropathy. PCR-RFLP was used to detect HSPG and ApoE genotypes in 385 Chinese subjects including 298 patients with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls (Non-DM). The T2DM group was subdivided into patients with (TDN; n = 218) and without diabetic nephropathy (Non-DN; n = 80). The latter group was further subdivided into groups of patients with microalbuminuria nephropathy (DN-1; n = 129) and severe diabetic nephropathy (DN-2; n = 89). We then compared the relative frequencies of various HSPG and ApoE genotypes and alleles among the groups, searching for predictive trends. The T allele of the HSPG gene occurred more frequently in the DN-2 group than in the Non-DN or DN-1 groups, their Fisher's exact p was 1.05 x 10(-3) and 6.58 x 10(-6); odds ratios were 2.09 (95% CI 1.32-3.30) and 2.48 (95% CI 1.64-3.74), respectively. The E2 allele of the ApoE gene occurred more frequently in the T2DM than in the Non-DM group, the Fisher's exact p was 0.0087; odds ratio was 3.45 (95% CI 1.30-9.81). Genotype analysis showed that the TT or TG of HSPG gene were paired with the E2/2 or E2/3 of ApoE gene significantly more frequently in the TDN group than in the Non-DN group, with an odds ratio of 3.03 (95% CI 1.03-8.90). There was no significant differences in other combinations of genotypes in HSPG and ApoE genes between TDN and Non-DN group. These results suggest that the HSPG T allele is a risk factor for the development of severe diabetic nephropathy in type 2 diabetic patients, and that the ApoE E2 allele is a risk factor for the occurrence of type 2 diabetes mellitus in Chinese general population. In addition, we find that co-inheritance of T/E2 confers a higher risk of type 2 diabetes mellitus progression to diabetic nephropathy in Chinese.

Aged↗

PubMed2001

Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study.

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex disease primarily caused by impairment in insulin sensitivity (SI) and insulin secretion. While a strong genetic component for T2DM is well established, there are few reports on racial differences in the magnitude of the genetic effects of T2DM and indices of glucose and insulin metabolism. We report here on the familial resemblance for traits related to glucose metabolism at pre-exercise training levels in 492 members from 99 sedentary White families and 259 members from 108 Black families participating in the multicenter HERITAGE Family Study. All these traits were obtained from the frequently sampled intravenous glucose tolerance test (IVGTT). They include glucose disappearance index (Kg), an overall index for glucose tolerance, acute insulin response to glucose (AIR(Glucose)) which is an index for insulin secretion, and those derived from the minimal model including SI and the disposition index (DI). DI, derived as the product of SI and AIR(Glucose), is a measure of the activity of the B-cells adjusted for insulin resistance. After adjustment for age, sex, and body mass index, the maximal heritability estimates in Blacks (Whites) are 48+/-14% (25+/-8%) for Kg, 44+/-14% (46+/-8%) for AIR(Glucose), 38+/-12% (44+/-8%) for SI and 32+/-14% (24+/-8%) for DI. Interestingly, Blacks have higher heritability for overall glucose tolerance than Whites but there is no race difference in heritability estimates for insulin sensitivity or insulin secretion.

Adult↗

PubMed2004

Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients.

OBJECTIVES: To study the effect of pioglitazone (PIO) on plasma resistin concentration, endogenous glucose production (EGP), and hepatic fat content (HFC) in patients with type II diabetes (T2DM). SUBJECTS: A total of 13 T2DM patients (age=51+/-2 y, BMI=29.7+/-1.1 kg/m(2), HbA(1c)=8.0+/-0.5%). METHODS: HFC (magnetic resonance spectroscopy) and basal plasma resistin concentration were quantitated before and after PIO treatment (45 mg/day) for 16 weeks. Subjects received a 3 h euglycemic insulin (100 mU/m(2)/min) clamp with 3-[(3)H] glucose to determine rates of EGP and tissue glucose disappearance (Rd) before and after PIO. RESULTS: PIO reduced fasting plasma glucose (10.3+/-0.7 to 7.6+/-0.6 mmol/l, P<0.001) and HbA(1c) (8.0+/-0.4 to 6.8+/-0.3%, P<0.001) despite increased body weight (83.2+/-3.4 to 86.3+/-3.4 kg, P<0.001). PIO improved Rd (4.9+/-0.4 to 6.6+/-0.5 mg/kg/min, P<0.005) and reduced EGP (0.22+/-0.04 to 0.06+/-0.02 mg/kg/min, P<0.01) during the insulin clamp. Following PIO, HFC decreased from 21.1+/-3.5 to 11.2+/-2.1% (P<0.005), and plasma resistin decreased from 5.3+/-0.6 to 3.5+/-0.3 ng/ml (P<0.01). Plasma resistin concentration correlated positively with HFC before (r=0.58, P<0.05) and after (r=0.55, P<0.05) PIO treatment. Taken collectively, plasma resistin concentration, before and after PIO treatment, correlated positively with hepatic fat content (r=0.66, P<0.001) and EGP during the insulin clamp (r=0.41, P<0.05). However, the plasma resistin concentration did not correlate with whole body glucose disposal (Rd) during the insulin clamp either before (r=-0.18, P=NS) or after (r=-0.13, P=NS) PIO treatment. CONCLUSIONS: PIO treatment in T2DM causes a significant decrease in plasma resistin concentration. The decrease in plasma resistin is positively correlated with the decrease in hepatic fat content and improvement in hepatic insulin sensitivity.

Blood Glucose↗

PubMed2005

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans.

OBJECTIVE: To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM). DESIGN: An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach. SUBJECTS: Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs. MEASUREMENTS: Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats. RESULTS: The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies. CONCLUSION: We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.

Adipose Tissue↗

PubMed2005

Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes.

INTRODUCTION: Obese and type 2 diabetic (T2DM) adolescents present with reduced insulin-stimulated glucose disposal and elevated intramyocellular lipids (IMCL) indicating comparable muscular insulin resistance and increased flux of free fatty acids (FFA) as in adult patients. In humans, the causal relationships between obesity and insulin resistance were examined in detail over the last years. METHODS: The impact of genetic factors was analyzed in young nonobese nondiabetic first-degree relatives of T2DM (REL-DM), whereas environmental factors were tested by challenging humans without genetic T2DM risk with lipid infusions or high-fat diets. RESULTS: REL-DM exhibit defects in mitochondrial oxidation and phosphorylation. Increased FFA availability results in accumulation of intramyocellular fatty acyl-CoA (FA-CoA) inducing a series of alterations: (i) inhibition of insulin signaling, (ii) reduction of insulin-(in)dependent glucose transport/phosphorylation, (iii) decreased insulin-stimulated glycogen synthesis, (iv) impaired insulin-stimulated oxidative phosphorylation (ATP synthesis), (v) accumulation of ectopic triglycerides (IMCL), (vi) reduced expression of peroxisome proliferator activated receptor gamma (PPARgamma) coactivator-1 (PGC-1) and PGC-1-controlled genes involved in mitochondrial biogenesis and oxidative phosphorylation and possibly also (vii) initiation of inflammatory processes by activation of PKC and nuclear factor-kappaB and decreased expression of matrix metalloproteinases (MMPs). CONCLUSIONS: The abnormalities could lead to a vicious cycle in which mitochondrial dysfunction, elevation of intramycellular lipids, impaired lipid oxidation and insulin resistance amplify each other. This is similar to the adaptive changes to fasting, which prevent energy loss during excessive FFA availability. The sequence of events may start with mitochondrial dysfunction in genetic insulin resistance and with increased intramyocellular lipids in environmental insulin resistance.

Adolescent↗

PubMed2003

Gliadin, endomysial and thyroid antibodies in patients with latent autoimmune diabetes of adults (LADA).

Latent autoimmune diabetes of adults (LADA) manifested after the age of 35 is characterized by the presence of disease-specific autoantibodies (anti-glutamate decarboxylase GADAb, anti-IA2Ab). However, autoimmunity in Type 1 diabetes mellitus is not targeted only to pancreatic beta-cells. No data have so far been published concerning the antibodies associated with other autoimmune disease in LADA patients. The presence of anti-thyroglobulin (TGAb), anti-thyroid peroxidase (TPOAb), anti-gliadin IgA (AGAAb) and IgG (AGGAb) and endomysial antibodies (EMAb) in sera of 68 diabetics typed as LADA was compared with the antibody presence in sera of 85 patients with Type 2 diabetes. We found a significantly higher occurrence of gliadin antibodies in LADA patients: the rate of AGGAb was 19.1% in comparison with 3.5% in the T2DM group (P = 0.0026), the rate of AGAAb was 13.2% in comparison with 3.5% (P = 0.035). The prevalence of EMAb was very low in both groups (1.5% and 0). The two groups differed significantly in the TPOAb rate: 22.1% in LADA compared to 9.4% in T2DM (P = 0.04), whereas no significant difference was found in the presence of TGAb (8.8% and 3.5%, P = 0.187). In comparison with T2DM patients, LADA patients were found to express higher antibody activity against gluten-related antigens and against TPO.

Age of Onset↗

PubMed2002

Clinical evidence of thiazolidinedione-induced improvement of pancreatic beta-cell function in patients with type 2 diabetes mellitus.

BACKGROUND: There is growing evidence in animal and in vitro studies showing that thiazolidinediones (TZDs) improve pancreatic beta cell (beta-cell) function. The aim of this study was to evaluate the effect of thiazolidinediones on the beta-cell function of patients with Type 2 diabetes mellitus (T2DM) in clinical practice. PATIENTS AND METHODS: This is an observational, nested case-control study. We identified 28 patients (TZD group), with T2DM, who had had a meal-stimulated C-peptide level documented before the addition of troglitazone to a failing double-therapy regimen with metformin (MET) and sulphonylurea (SU). As a control group (CTRL), we identified 26 patients, with T2DM, who also had had a meal-stimulated C-peptide documented before adding MET to a failing SU monotherapy regimen. We then proceeded to prospectively remeasure their meal-stimulated C-peptide levels and compared the changes over time between the two groups. RESULTS: Both groups were well matched for age, body mass index (BMI), and HgbA1c before and after treatment. The C-peptide in the TZD group increased significantly during therapy (from 3.2 +/- 0.5 to 4.2 +/- 0.5, p = 0.01), whereas it remained unchanged in the CTRL group (from 4.8 +/- 0.6 to 5.0 +/- 0.5, p = 0.74). The C-peptide/glucose ratio also increased significantly in the TZD group (from 1.9 +/- 0.3 to 3.1 +/- 0.3, p = 0.0003) whereas it remained unchanged in the CTRL group (from 3.4 +/- 0.7 to 3.4 +/- 0.3, p = 0.97). Furthermore, the C-peptide/glucose ratio of the TZD group, which was significantly lower at baseline compared with the CTRL group (1.9 +/- 0.3 vs. 3.4 +/- 0.7, p = 0.04), caught up to its level during treatment (3.1 +/- 0.3 vs. 3.4 +/- 0.3, p = 0.48). CONCLUSION: Thiazolidinediones seem to induce recovery of pancreatic beta cell function, independently of the correction of glucose toxicity.

Biomarkers↗

PubMed2003

Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.

AIM: These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2DM) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2DM who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue. METHODS: Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2DM patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm(-2), 25-30 kgm(-2), >30 kgm(-2) respectively). RESULTS: RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: -16% and +19%; 8 mg: -37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese. CONCLUSIONS: In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.

Adult↗