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PubMed2006

Comprehensive assessment of postischemic vascular reactivity in Hispanic children and adults with and without diabetes mellitus.

BACKGROUND: To examine the whole postischemic hyperemic response period in Hispanic children and adults with and without type 2 diabetes mellitus (T2DM) and offer insight into the potential adaptive mechanisms involved in the arterial response to disturbances in vascular homeostasis. METHODS: Ninety-eight adults and 124 children of Hispanics participated in the study. Endothelial function was assessed in the brachial artery using high-resolution ultrasonography (HRU). A continuous scan was taken for 5 min during the hyperemic response, flow velocity (FV) recordings and diameter measurements were obtained, and brachial arterial blood flow (BF) was calculated after the cuff deflation. RESULTS: The increment in FV during the reactive hyperemic period was higher in obese and in diabetic children than in lean healthy children, although the time to reach peak brachial artery diameter (BAD) and the per cent increase in peak diameter were comparable in all three groups. In subjects with impaired glucose tolerance (IGT), the hyperemic peak increase in FV was comparable to those in healthy adults. In diabetic patients, the peak increase in BAD as well as the per cent increment in the diameter were reduced at 50-60 s after the release of the arm cuff. The time to reach the peak increase in diameter also was prolonged in diabetics when compared with healthy adults. CONCLUSION: Our study demonstrates clear differences in the normal vascular response between healthy children and healthy adults and discloses the presence of additional abnormalities in the flow-mediated vasodilation in diabetic and 'prediabetic' subjects.

Adult↗

PubMed2005

Genetic and clinical characteristics of maturity-onset diabetes of the young.

Genetic factors play an important role in various forms of diabetes mellitus (DM), but inheritance is complex and interacts with environmental factors. Although in most cases type 2 DM (T2DM) and T1DM are polygenic disorders, several monogenic forms have been identified. Among them, maturity-onset diabetes of the young (MODY) has been the most intensively investigated. MODY is a group of six different forms of monogenic diabetes, characterized by insulin secretion defects in pancreatic beta-cells, supposed to be responsible for 2-5% of all cases of diabetes. The most common are MODY2 and MODY3, caused by mutations in the genes encoding glucokinase and hepatocyte nuclear factor 1-alpha respectively. MODY2 is characterized by glucose sensing defects, leading to an increase in insulin secretion threshold. This causes lifelong sustained and mild hyperglycaemia from birth, most often in non-diabetic levels. Diagnosis is incidental in most cases. These patients are asymptomatic, seldom need treatment and rarely present chronic complications. MODY3 is characterized by a severe insulin secretion defect in response to glucose. Diagnosis is made usually in adolescence and early adulthood, often by osmotic symptoms. Hyperglycaemia is progressive, and patients frequently need treatment with oral drugs or insulin some time in their follow up. This group seems to have a marked sensitivity to sulphonylureas compared to other types of diabetes. The recognition of MODY as a monogenic disorder and a thorough understanding of its pathophysiology are important for correct diagnosis and treatment, with great impact on prognosis. Besides, the study of these forms of diabetes brings important contributions to the understanding of glucose homeostasis as a whole.

Adolescent↗

PubMed2005

Type 2 diabetes in rural and urban population: diverse prevalence and associated risk factors in Bangladesh.

AIMS: To describe differences in prevalence of Type 2 diabetes mellitus with its associated risk factors between rural and urban populations in Bangladesh. Diagnostic criteria [fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT)] were compared and reviewed for both populations. METHODS: A total of 1555 subjects from urban and 4757 from rural communities (age > or = 20 years) with similar cultural and ethnic backgrounds were randomly selected in a cross-sectional survey. FBG values were determined from all and 2-h post-glucose capillary blood samples were determined after a 75-g oral glucose load for a selected number (urban 476, rural 1046). RESULTS: A higher prevalence of diabetes was found in urban (8.1%) compared with rural populations (2.3%). Age, sex and waist-to-hip ratio for men were significant risk factors for both urban and rural subjects following fasting and 2-h post-glucose values adjusted for a number of confounding variables. Poor agreement was observed between FBG and OGTT for both urban (kappa 0.41) and rural (kappa 0.40) areas. CONCLUSIONS: A higher prevalence of diabetes mellitus (DM) in the urban population was observed compared with rural subjects despite similar body mass indexes (BMI). Differences in obesity, waist/hip ratio or hypertension failed to explain the increasing occurrence of T2DM in the urban population.

Adult↗

PubMed2006

Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: the Diabetes Heart Study.

AIMS: Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). METHODS: Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. RESULTS: Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. CONCLUSIONS: Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.

Adult↗

PubMed2004

A genome scan for diabetic nephropathy in African Americans.

BACKGROUND: There is substantial evidence for a genetic contribution to diabetic nephropathy susceptibility in the African American population, but little is known about location or identity of susceptibility genes. METHODS: DNA samples were collected from 206 type 2 diabetes (T2DM) and end-stage renal disease (ESRD)/nephropathy-affected sib pairs from 166 African American families (355 affected individuals). A genome scan was performed and data analyzed using nonparametric linkage regression (NPLR) analysis and ordered subsets analysis (OSA) methods. RESULTS: In initial NPLR analyses no logarithm of odds (LOD) scores >2.0 were observed. Four loci had LOD scores > or =1.0, with LOD = 1.43 at 29 cM on chromosome 7p the highest. NPLR analyses of multilocus interactions detected 6 loci (7p, 12p, 14q, 16p, 18q, and 21q) with LOD scores 1.15 to 1.63. NPLR analyses evaluating phenotypic interactions revealed multiple locations with evidence (P < 0.05) for interactions with age-at-onset of ESRD (9 loci), duration of diabetes before onset of ESRD (19 loci), and age-at-onset of diabetes (14 loci). Several loci identified by NPLR analyses were also identified using OSA. OSA revealed evidence for a nephropathy locus at 135 cM on chromosome 3 in an estimated 29% of the families (LOD = 4.55 in the optimal subset). Additional linkage evidence, LOD = 3.59, was observed on chromosome 7p (37% of the families, longer duration of diabetes prior to diagnosis of ESRD), and 18q (max. LOD = 3.72; 64% of the families, early diabetes diagnosis). The 7p linkage has been observed in a recent genome scan of African American type 2 diabetes. CONCLUSION: This first genome scan of diabetic nephropathy in African Americans reveals evidence for susceptibility loci on chromosomes 3q, 7p, and 18q. The 7p locus may represent a type 2 diabetes susceptibility locus.

Adult↗

PubMed2004

Detecting and managing patients with type 2 diabetic kidney disease: proteinuria and cardiovascular disease.

BACKGROUND: The increasing prevalence of type 2 diabetes (T2DM) places more patients at risk for developing chronic kidney disease (CKD) or cardiovascular (CV) events. Effective therapy for CKD or CV disease (CVD) requires a method of identifying affected patients and monitoring the effectiveness of therapy. METHODS: We tested the predictive value of proteinuria for identifying patients at risk for progressive CDK and CVD, and monitoring treatment was determined using RENAAL study results. RESULTS: Baseline proteinuria identified patients at risk for progressive CKD and CVD. Suppression of proteinuria was associated with decreased likelihood of CKD or CVD. CONCLUSION: Proteinuria identifies the risk of CKD and CVD, and can be used to monitor the effectiveness of therapy.

Cardiovascular Diseases↗

PubMed2006

Rosiglitazone is effective and well-tolerated in a range of therapeutic regimens during daily practice in patients with type 2 diabetes.

Subjects (N = 22,808) with inadequately controlled type 2 diabetes mellitus (T2DM) were included in a large 6-month observational study in Germany. Rosiglitazone (RSG) was added to existing therapy in line with daily practice, with 19,962 subjects evaluated for efficacy by treatment group: RSG monotherapy (n = 1017), RSG plus metformin (MET) (n = 7160), RSG plus sulphonylurea (n = 5033), triple oral therapy (n = 4247), and the remaining subject population (n = 2505). Overall, RSG significantly reduced median HbA(1c) and fasting blood glucose by 1.3% and 50 mg/dl over 6 months (p < 0.001 for both). The proportion of subjects achieving glycaemic goals of <or= 6.5% and <or= 7.0% increased from 5.7% to 33.8%, and from 13.9% to 55.5%, respectively (p < 0.001 for both). Mean systolic and diastolic blood pressures were reduced in the total subject population by 6 mmHg and 2 mmHg, respectively (p < 0.001 for both). RSG had a neutral or reductive effect on mean weight of most (69%) subjects. Consistent with clinical trial data, RSG mono- or combination therapy improved glycaemic control when used in daily clinical practice and is generally well-tolerated.

Blood Glucose↗

PubMed2006

Association of selective HLA class II susceptibility-conferring and protective haplotypes with type 2 diabetes in patients from Bahrain and Lebanon.

The association of HLA class II with type 2 diabetes (T2DM) was investigated in Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201 (Lebanese) were susceptibility-conferring alleles, and unique susceptibility-conferring/protective haplotypes were found in both patient groups. Regression analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101-DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes.

Alleles↗

PubMed2006

Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle.

Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and calorie restriction. Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control and 20 exercise trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys (Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.

Animals↗

PubMed2003

Increased frequency of HLA A2/DR4 and A2/DR8 haplotypes in young saskatchewan aboriginal people with diabetic end-stage renal disease.

AIMS: To determine the association of HLA with diabetic end-stage renal disease (DESRD) in Saskatchewan aboriginal people. METHODS: This was a retrospective study of HLA profiles in four groups of Saskatchewan residents with ESRD diagnosed from 1980 to 1998: aboriginal people with and without DESRD, and non-aboriginal people with and without DESRD. The aboriginal DESRD group was also subdivided into those 50 years of age. Frequencies of individual and combinations of HLA antigens were compared between groups and subgroups. RESULTS: HLA data were available for 634 subjects. Young aboriginal people with DESRD had a higher frequency of HLA-A2 than older AB DESRD subjects (69 vs. 36%; p = 0.03), and of HLA-DR4 and/or DR8 compared to older AB DESRD subjects (91 vs. 68%; p = 0.07) and AB non-DESRD subjects (91 vs. 67%; p = 0.03). Over 65% of young AB DESRD subjects had either an A2/DR4 or A2/DR8 haplotype (odds ratio 5.09 [confidence intervals 1.35, 20.15] versus older AB DESRD subjects; odds ratio 3.32 [confidence intervals 1.20, 9.3] versus AB non-DESRD subjects). Forty percent of young AB DESRD subjects were homozygous for at least one of A2, DR4 or DR8. CONCLUSIONS: Our findings suggest that DESRD in young AB subjects with T2DM has a genetic basis related to HLA.

Adult↗

PubMedDate not supplied

Barriers to medical nutrition therapy in black women with type 2 diabetes mellitus.

PURPOSE: The purpose of this study was to explore food purchasing, preparation, and consumption among black women with type 2 diabetes mellitus (T2DM) in an urban setting to assess barriers to medical nutrition therapy recommendations. METHODS: A telephone survey was developed to assess shopping habits, the use of community resources for food supplementation, use of restaurant/fast-food establishments, dining habits, food purchasing and consumption, and food preparation methods. This 38-item questionnaire provided both frequencies and trends regarding participants' dietary habits. RESULTS: Black women identified ways in which their participation in a culturally competent intervention of diabetes care and education helped them to change dietary behaviors. The most common areas of change included purchasing, preparation, and portion size. Barriers to medical nutrition therapy identified included low income, time constraints, competing demands, and knowledge deficits. CONCLUSIONS: Culturally sensitive diabetes interventions are an effective way to overcome some of the barriers to medical nutrition therapy. Feedback provided by this survey suggests that identification of more affordable healthy food resources in the community is necessary. In addition, access issues such as transportation to grocery stores should be on the agenda for public policy issues. Finally, alternate sites for nutrition education, such as a supermarket forum, warrant further investigation.

Black People↗

PubMed2024

No causal relationship between glucose and inflammatory bowel disease: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. RESULTS: We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649-1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn's disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628-1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits. CONCLUSIONS: This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it's subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.

Humans↗

PubMed2006

Reduced CD4+ subset and Th1 bias of the human iNKT cells in Type 1 diabetes mellitus.

Invariant NKT (iNKT) cells are considered to be important in some autoimmune diseases including Type 1 diabetes mellitus (T1DM). So far, the published data are contradictory in regard to the role of iNKT cells in T1DM. We aimed to study iNKT cell frequency and the function of different iNKT cell subgroups in T1DM. We compared the results of four subject groups: healthy (H), long-term T2DM (ltT2DM; more than 1 year), newly diagnosed T1DM (ndT1DM; less than 3 months), and ltT1DM (more than 1 year) individuals. We measured the iNKT cell frequencies by costaining for the invariant TCR alpha-chain with 6B11-FITC and Valpha24-PE. After sorting the Valpha24+6B11+ cells, the generated iNKT clones were characterized. We tested CD4, CD8, and CD161 expression and IL-4 and IFN-gamma production on TCR stimulation. The CD4+ population among the iNKT cells was decreased significantly in ltT1DM versus ndT1DM, ltT2DM, or H individuals. The T1DM iNKT cell cytokine profile markedly shifted to the Th1 direction. There was no difference in the frequency of iNKT cells in PBMC among the different patient groups. The decrease in the CD4+ population among the iNKT cells and their Th1 shift indicates dysfunction of these potentially important regulatory cells in T1DM.

Adult↗

PubMed2003

IA-2 autoantibodies are predominant in latent autoimmune diabetes in adults patients from eastern India.

Autoimmune diabetes or latent autoimmune diabetes in adults (LADA) among the clinically diagnosed type 2 diabetes patients from Cuttack in Eastern India was studied. GAD65 and IA-2 autoantibodies were measured by radioligand binding assay using recombinant human GAD65 and IA-2. The frequency of GAD65 was not significantly different between patients and controls. However, IA-2 antibodies were predominant in LADA patients and there were two distinct peaks, one in the age group of 20 to 30 years and another in the age group of 50 to 60 years. The data suggest that LADA is more frequent in Eastern Indian T2DM patients and the IA-2 is the predominant autoantibody in this population.

Adult↗

PubMed2004

PPAR-gamma2 Pro12Ala variant is associated with greater insulin sensitivity in childhood obesity.

Several genetic variants of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a molecule known to be involved in transcription of target genes, have been identified. Pro12Ala, a missense mutation in exon 2 of the gene, is highly prevalent in Caucasian populations. Conflicting conclusions about the association between this mutation and complex traits such as obesity, insulin sensitivity, and T2DM have been reported. We have investigated the association of PPAR-gamma2 Pro12Ala polymorphism with measures of insulin sensitivity in a population of Italian obese children (n = 200; mean age, 10.38 +/- 2.8 y) in whom clinical and biochemical analyses were performed. To estimate the insulin sensitivity status, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all subjects. The effect of the Pro12Ala polymorphism on quantitative variables was tested using multiple linear regression analysis. The frequency of Ala carriers was 17%, similar to that reported in other adult Caucasian populations. The X12Ala (either Pro12Ala or Ala12Ala) genotype was associated with significantly lower fasting insulin levels compared with Pro/Pro (p = 0.008). Consistent with this finding, significantly lower HOMA-IR was observed in X12Ala carriers (p = 0.023). In conclusion, our observations demonstrate that the X12Ala variant is significantly associated with greater insulin sensitivity in childhood obesity. Because obesity is one of the most important risk factors for cardiovascular diseases and type 2 diabetes, obese children, who are presumably at a higher risk, may be protected from these diseases by the phenotypic effect of the Ala 12 allele on insulin resistance.

Adolescent↗

PubMed2006

School-based intervention acutely improves insulin sensitivity and decreases inflammatory markers and body fatness in junior high school students.

CONTEXT: Risk factors for type 2 diabetes mellitus (T2DM) include obesity, family history, dyslipidemia, a proinflammatory state, impaired insulin secretory capacity, and insulin resistance. OBJECTIVE: The aim of this study was to examine the effects of a 3- to 4-month school-based intervention consisting of health, nutrition, and exercise classes plus an aerobic exercise program on diabetes risk. DESIGN: This study was a randomized before/after controlled trial. METHODS: Seventy-three eighth-grade students in a predominantly Hispanic New York City public school were divided into a control group (studied twice without receiving the intervention) and an experimental group (studied before and after the intervention). OUTCOME MEASURES: We measured body fatness (bioelectrical impedance), insulin sensitivity, beta-cell function (insulin release in response to an iv glucose load corrected for insulin sensitivity), lipid profiles, and circulating concentrations of IL-6, C-reactive protein, adiponectin, and TNF-alpha. RESULTS: Participation in the intervention was associated with significant reductions in body fatness, insulin resistance, and circulating concentrations of C-reactive protein and IL-6, irrespective of somatotype on enrollment. CONCLUSION: Short-term school-based health, nutrition, and exercise intervention is beneficial to all students and affects multiple diabetes risk factors.

Adolescent↗

PubMed2024

Genomic variants associated with type 2 diabetes mellitus among Filipinos.

Type 2 diabetes mellitus leads to debilitating complications that affect the quality of life of many Filipinos. Genetic variability contributes to 30% to 70% of T2DM risk. Determining genomic variants related to type 2 diabetes mellitus susceptibility can lead to early detection to prevent complications. However, interethnic variability in risk and genetic susceptibility exists. This study aimed to identify variants associated with type 2 diabetes mellitus among Filipinos using a case-control design frequency matched for age and sex. A comparison was made between 66 unrelated Filipino adults with type 2 diabetes mellitus and 121 without. Genotyping was done using a candidate gene approach on genetic variants of type 2 diabetes mellitus and its complications involving allelic association and genotypic association studies with correction for multiple testing. Nine (9) significant variants, mostly involved in glucose and energy metabolism, associated with type 2 diabetes mellitus in Filipinos were found. Notably, a CDKAL1 variant (rs7766070) confers the highest level of risk while rs7119 (HMG20A) and rs708272 (CETP) have high risk allele frequencies in this population at 0.77 and 0.66, respectively, making them potentially good markers for type 2 diabetes mellitus screening. The data generated can be valuable in developing genetic risk prediction models for type 2 diabetes mellitus to diagnose and prevent the condition among Filipinos.

Humans↗

PubMed2006

[Insulin resistance and metabolic syndrome in type 1 diabetes mellitus].

Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40% in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.

Cardiovascular Diseases↗