Age of onset of obesity and risk of type 2 diabetes

OBJECTIVE: To compare a simple measure - age of onset of obesity - to an obese-years construct (a product of duration and magnitude of obesity) as risk factors for type 2 diabetes.

METHOD: Participants from the Framingham Heart Study who were not obese and did not have diabetes at baseline were included (n=4,320). The Akaike Information Criterion (AIC) was computed to compare four Cox proportional hazards models with incident diabetes as the outcome and: (i) obese-years; (ii) age of onset of obesity; (iii) body mass index (BMI); and (iv) age of onset of obesity plus magnitude of BMI combined, as exposures.

RESULTS: AIC indicated that the model with obese-years provided a more effective explanation of incidence of type 2 diabetes compared to the remaining three models. Models including age of onset of obesity plus BMI were not appreciably different from the model with BMI alone, except in those aged ≥60.

CONCLUSIONS: While obese-years was the optimal obesity construct to explain risk of type 2 diabetes, age of onset may be a useful, practical addition to current BMI in the elderly.

IMPLICATIONS: Where computation of obese-years is not possible or impractical, age of onset of obesity combined with BMI may provide a useful alternative.

Assessment of Health-Related Quality of Life using the EQ-5D-3L in Individuals with Type 2 Diabetes Mellitus

The daily experience with type 2 diabetes mellitus (T2DM) has significant adverse effects on health-related quality of life (HRQoL). HRQoL assessment is essential for measuring the impact of the disease on the patient and selecting individualized strategies. Generic measures for assessing HRQoL are very useful because, unlike specific measurement instruments, they allow for the comparison with other instruments. The EQ-5D-3L is a generic measure and it describes HRQoL in five dimensions; mobility, self-care, usual activities, pain/discomfort and anxiety/depression, with three levels each. In Portugal, studies using the EQ-5D-3L as a generic measure to assess HRQoL in diabetic patients are scarce. Objective: To assess HRQoL in individuals with T2DM using the Portuguese version of the EQ-5D-3L. Methodology: An accidental sample of patients with T2DM (n=437) was selected at Family Health Units and healthcare centers in Coimbra, Portugal, between January 2013 and January 2014. The EQ-5D-3L was applied in interviews. The EQ-5D-3L score was calculated based on the answers to the five dimensions and the value system for the Portuguese population. Results: In this sample, 100% of the participants answered the EQ-5D-3L. The HRQoL score was 0.6772 in the EQ-5D-3L and 64.85 in the EQ-VAS. The most frequent answers to the five dimensions were no problems or some problems. The mean score of the EQ-5D-3L was significantly associated with age, male gender, high level of education, having an occupation, practicing physical activity, being single and having been diagnosed with T2DM for less time. The Cronbach alpha's value was 0.674, confirming an acceptable internal consistency. Conclusion: HRQoL levels in individuals with T2DM are lower than the national average and vary depending on sociodemographic and clinical characteristics. The EQ-5D-3L is a reliable instrument that can be used to assess the quality of life of diabetic patients and contribute to assess the patients' overall health status, adding data from the subjective dimension of self-care management.

Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit

Background: Obesity is increasingly prevalent in many countries. Obesity is a major risk factor for the development of type 2 diabetes but its relationship with diabetic kidney disease (DKD) remains unclear. Some studies have suggested that the metabolic syndrome (including obesity) may be associated with DKD in type 1 diabetes. Aim: To investigate the association between obesity and DKD. Design: Retrospective cross-sectional study. Methods: National Diabetes Audit data were available for the 2007–08 cycle. Type 1 and 2 diabetes patients with both a valid serum creatinine and urinary albumin:creatinine ratio were included. DKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, albuminuria or both. Logistic regression was used to analyse associations of obesity (body mass index ≥30 kg/m2) and other variables including year of birth, year of diagnosis, ethnicity and stage of kidney disease. Results: A total of 58 791 type 1 and 733 769 type 2 diabetes patients were included in the analysis. After adjustment, when compared with type 1 diabetes patients with normal renal function those with DKD were up to twice as likely to be obese. Type 2 DKD patients were also more likely to be obese. For example, type 2 diabetes patients with an eGFR <15 ml/min/1.73 m2 and normoalbuminuria, microalbuminuria or macroalbuminuria were all more likely to be obese; odds ratios (95% CI) 1.65 (1.3–2.1), 1.56 (1.28–1.92) and 1.27 (1.05–1.54), respectively. Conclusions: This study has highlighted a strong association between obesity and kidney disease in type 1 diabetes and confirmed their association in type 2 diabetes.

Lipid profile of people with Diabetes mellitus type 2 and periodontal disease

The objective of this study was to evaluate improvement of lipids and periodontal disease in patients with type 2 Diabetes mellitus, by means of the relationship between blood levels of total cholesterol and its fractions, triglycerides and clinical periodontal parameters. Twenty patients, in age-range 18-70 years, were selected and divided into 2 groups: (1) conventional periodontal scaling and root planing + controlled mechanic; (2) conventional periodontal scaling and root planing + controlled mechanical + maintenance therapy. The analyses were performed on day 0, 180 and 720 days, including plaque index, gingival index, probing depth and clinical attachment level, and evaluation of total cholesterol and its fractions, and triglycerides. The 2 groups presented significant reduction in clinical periodontal parameters, however, probing depth did not diminish significantly only in Group 1. There was significant improvement in all blood parameters in both groups. It was concluded that after 720 days of the experiment, there were significant improvements in clinical and blood parameters, in general. The group that received maintenance therapy also showed a more expressive improvement in clinical periodontal parameters, in general, suggesting that this therapy is important and necessary in patients with type 2 Diabetes mellitus and periodontal disease. (C) 2011 Elsevier B.V. All rights reserved.

Prevalence and antifungal resistance profile of Candida spp. oral isolates from patients with type 1 and 2 diabetes mellitus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of the mRNA expression of the S100 beta protein in adipocytes of patients with diabetes mellitus, type 2

Objective: This study aims to explore the possible relationship between the expression level of S100 beta protein mRNA with diabetes mellitus type 2 in adipocytes from patients with this disease in comparison with normoglycemic individuals. Materials and methods: Samples of adipose tissue of eight patients from the coronary section of the Institute Dante Pazzanese of Cardiology (IDPC), four in Group Diabetes and four of Normoglycemic group, were evaluated by RT-PCR real time. Results: An increase around 15 times values, between the threshold cycle (Delta Ct), of mRNA expression of S100 beta protein in adipocytes of the diabetes group was observed in comparison to the control group (p = 0.015). Conclusion: Our results indicate, for the first time, that there is coexistence of increased expression of the S100 beta and the type 2 diabetes mellitus gene. Arq Bras Endocrinol Metab. 2012;56(7):435-40

Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

Abstract Background Regardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics. Results The use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis. Conclusions These results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.

Resistance training for obese, type 2 diabetic adults: A review of the evidence

In both developed and developing countries, increased prevalence of obesity has been strongly associated with increased incidence of type 2 diabetes mellitus (T2DM) in the adult population. Previous research has emphasized the importance of physical activity in the prevention and management of obesity and T2DM, and generic exercise guidelines originally developed for the wider population have been adapted for these specific populations. However, the guidelines traditionally focus on aerobic training without due consideration to other exercise modalities. Recent reviews on resistance training in the T2DM population have not compared this modality with others including aerobic training, or considered the implications of resistance training for individuals suffering from both obesity and T2DM. In short, the optimal mix of exercise modalities in the prescription of exercise has not been identified for it benefits to the metabolic, body composition and muscular health markers common in obesity and T2DM. Similarly, the underlying physical, social and psychological barriers to adopting and maintaining exercise, with the potential to undermine the efficacy of exercise interventions, have not been addressed in earlier reviews. Because it is well established that aerobic exercise has profound effects on obesity and T2DM risk, the purpose of this review was to address the importance of resistance training to obese adults with T2DM.

The impact of the metabolic syndrome and parental risk factors in patients with type 1 diabetes

Background: One-third of patients with type 1 diabetes develop diabetic complications, such as diabetic nephropathy. The diabetic complications are related to a high mortality from cardiovascular disease, impose a great burden on the health care system, and reduce the health-related quality of life of patients. Aims: This thesis assessed, whether parental risk factors identify subjects at a greater risk of developing diabetic complications. Another aim was to evaluate the impact of a parental history of type 2 diabetes on patients with type 1 diabetes. A third aim was to assess the role of the metabolic syndrome in patients with type 1 diabetes, both its presence and its predictive value with respect to complications. Subjects and methods: This study is part of the ongoing nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. The study was initiated in 1997, and, thus far, 4,800 adult patients with type 1 diabetes have been recruited. Since 2004, follow-up data have also been collected in parallel to the recruitment of new patients. Studies I to III have a cross-sectional design, whereas Study IV has a prospective design. Information on parents was obtained from the patients with type 1 diabetes by a questionnaire. Results: Clustering of parental hypertension, cardiovascular disease, and diabetes (type 1 and type 2) was associated with diabetic nephropathy in patients with type 1 diabetes, as was paternal mortality. A parental history of type 2 diabetes was associated with a later onset of type 1 diabetes, a higher prevalence of the metabolic syndrome, and a metabolic profile related to insulin resistance, despite no difference in the distribution of human leukocyte antigen genotypes or the presence of diabetic complications. A maternal history of type 2 diabetes, seemed to contribute to a worse metabolic profile in the patients with type 1 diabetes than a paternal history. The metabolic syndrome was a frequent finding in patients with type 1 diabetes, observed in 38% of males and 40% of females. The prevalence increased with worsening of the glycemic control and more severe renal disease. The metabolic syndrome was associated with a 3.75-fold odds ratio for diabetic nephropathy, and all of the components of the syndrome were independently associated with diabetic nephropathy. The metabolic syndrome, independent of diabetic nephropathy, increased the risk of cardiovascular events and cardiovascular and diabetes-related mortality over a 5.5-year follow-up. With respect to progression of diabetic nephropathy, the role of the metabolic syndrome was less clear, playing a strong role only in the progression from macroalbuminuria to end-stage renal disease. Conclusions: Familial factors and the metabolic syndrome play an important role in patients with type 1 diabetes. Assessment of these factors is an easily applicable tool in clinical practice to identify patients at a greater risk of developing diabetic complications.

Diabetic cardiomyopathy and post-infarct ventricular remodelling : Effects of levosimendan in a rodent model of type II diabetes

Type 2 diabetes is a risk factor for the development of cardiovascular disease. Recently, the term diabetic cardiomyopathy has been proposed to describe the changes in the heart that occur in response to chronic hyperglycemia and insulin resistance. Ventricular remodelling in diabetic cardiomyopathy includes left ventricular hypertrophy, increased interstitial fibrosis, apoptosis and diastolic dysfunction. Mechanisms behind these changes are increased oxidative stress and renin-angiotensin system activation. The diabetic Goto-Kakizaki rat is a non-obese model of type 2 diabetes that exhibits defective insulin signalling. Recently two interconnected stress response pathways have been discovered that link insulin signalling, longevity, apoptosis and cardiomyocyte hypertrophy. The insulin-receptor PI3K/Ak pathway inhibits proapoptotic FOXO3a in response to insulin signalling and the nuclear Sirt1 deacetylase inhibits proapoptotic p53 and modulates FOXO3a in favour of survival and growth. --- Levosimendan is a calcium sensitizing agent used for the management of acute decompensated heart failure. Levosimendan acts as a positive inotrope by sensitizing cardiac troponin C to calcium and exerts vasodilation by opening mitochondrial and sarcolemmal ATP-sensitive potassium channels. Levosimendan has been described to have beneficial effects in ventricular remodelling after myocardial infarction. The aims of the study were to characterize whether diabetic cardiomyopathy associates with cardiac dysfunction, cardiomyocyte apoptosis, hypertrophy and fibrosis in spontaneously diabetic Goto-Kakizaki (GK) rats, which were used to model type 2 diabetes. Protein expression and activation of the Akt FOXO3a and Sirt1 p53 pathways were examined in the development of ventricular remodelling in GK rats with and without myocardial infarction (MI). The third and fourth studies examined the effects of levosimendan on ventricular remodelling and gene expression in post-MI GK rats. The results demonstrated that diabetic GK rats develop both modest hypertension and features similar to diabetic cardiomyopathy including cardiac dysfunction, LV hypertrophy and fibrosis and increased apoptotic signalling. MI induced a sustained increase in cardiomyocyte apoptosis in GK rats together with aggravated LV hypertrophy and fibrosis. The GK rat myocardium exhibited decreased Akt- FOXO3a phosphorylation and increased nuclear translocation of FOXO3a and overproduction of the Sirt1 protein. Treatment with levosimendan decreased cardiomyocyte apoptosis, senescence and LV hypertrophy and altered the gene expression profile in GK rat myocardium. The findings indicate that impaired cardioprotection via Akt FOXO3a and p38 MAPK is associated with increased apoptosis, whereas Sirt1 functions in counteracting apoptosis and the development of LV hypertrophy in the GK rat myocardium. Overall, levosimendan treatment protects against post-MI ventricular remodelling and alters the gene expression profile in the GK rat myocardium.

Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles

Metabonomics, the study of metabolites and their roles in various disease states, is a novel methodology arising from the post-genomics era. This methodology has been applied in many fields, including work in cardiovascular research and drug toxicology. In this study, metabonomics method was employed to the diagnosis of Type 2 diabetes mellitus (DM2) based on serum lipid metabolites. The results suggested that serum fatty acid profiles determined by capillary gas chromatography combined with pattern recognition analysis of the data might provide an effective approach to the discrimination of Type 2 diabetic patients from healthy controls. And the applications of pattern recognition methods have improved the sensitivity and specificity greatly. (C) 2004 Elsevier B.V. All rights reserved.

Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation

Background: Nateglinide restores early-phase insulin secretion to feeding and reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose-dependent insulinotropic polypeptide (GIP) degradation

Meal-induced 24-hour profile of circulating glycated insulin in type 2 diabetic subjects measured by a novel radioimmunoassay

Increasing evidence supports a role for glycated insulin in the insulin-resistant state of type 2 diabetes. We measured 24-hour profiles of plasma glycated insulin, using a novel radioimmunoassay (RIA), to evaluate the effects of meal stimulation and intermittent fasting on circulating concentrations of plasma glycated insulin in type 2 diabetes. Patients (n = 6; hemoglobin A(1c) [HbA(1c)], 7.2% +/- 0.6%; fasting plasma glucose, 7.4 +/- 0.7 mmol/L; body mass index [BMI], 35.7 +/- 3.5 kg/m(2); age, 56.3 +/- 4.4 years) were admitted for 24 hours and received a standardized meal regimen. Half-hourly venous samples were taken for plasma glycated insulin, glucose, insulin, and C-peptide concentrations between 8 Am and midnight and 2-hourly overnight. The mean plasma glycated insulin concentration over 24 hours was 27.8 +/- 1.2 pmol/L with a mean ratio of insulin:glycated insulin of 11:1. Circulating glucose, insulin, C-peptide, and glycated insulin followed a basal and meal-related pattern with most prominent increments following breakfast, lunch, and evening meal, respectively. The mean concentrations of glycated insulin during the morning, afternoon, evening, and night-time periods were 24.4 +/- 2.5, 28.7 +/- 2.3, 31.1 +/- 2.1, and 26.2 +/- 1.5 pmol/L, respectively, giving significantly higher molar ratios of insulin:glycated insulin of 18.0:1, 14.2:1, and 12.7:1 compared with 7.01 at night (P

SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

AIMS/HYPOTHESIS: Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. METHODS: We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. RESULTS: In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p?=?0.00045, p (36tests)?=?0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p?=?0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p?=?0.0040), but the association did not remain after Bonferroni correction (p (36tests)?=?0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. CONCLUSIONS/INTERPRETATION: A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.

New susceptibility Loci associated with kidney disease in type 1 diabetes

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P?=?1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P?=?2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P?=?2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.