First-degree Relatives Of Type Research Articles

The role of high fat diet on serum uric acid level among healthy male first degree relatives of type 2 diabetes mellitus

First-degree relatives (FDR) of type 2 diabetes mellitus have increased risk of developing insulin resistance-related disorders including hyperuricemia. We investigated metabolic profile and serum uric acid (SUA) metabolism in response to high-fat diet among healthy male FDR in comparison to those without family history of diabetes. A total of 30 FDR and 30 non-FDR subjects completed a 5-days-hypercaloric diet with fat added to regular daily intake. Despite similar insulin response, FDR displayed different changes in SUA compared to non-FDR subjects (0.26 ± 0.83 mg/dL vs − 0.21 ± 0.78 mg/dL, p = 0.028). In subgroup analyses stratified by body mass index and waist circumference, significant different SUA changes between FDR and non-FDR subjects were only found in obese (0.48 ± 0.87 mg/dL vs − 0.70 ± 0.71 mg/dL, p = 0.001) and centrally obese (0.59 ± 0.83 mg/dL vs − 0.55 ± 0.82 mg/dL, p = 0.011) subgroups. In multivariate analysis, visceral adiposity seemed mediating the different response in SUA metabolism between FDR and non-FDR subjects induced by short-term obesogenic diet.

Study of Serum Adipocytokines and Lipid Profile with Leptin/Adiponectin Ratio in First-Degree Relatives of Type 2 Diabetic Patients

Background: The primary health issues worldwide which silently kill are Type 2 Diabetes Mellitus and obesity with the prevalence range of respectfully. The adipose tissue functions play a critical role mainly in glucose and lipid homeostasis. The expansion of the adipocyte mainly leads to chronic low-grade inflammation by the release of pro-inflammatory cytokines such as adiponectin & leptin and others. The adiponectin has anti-atherogenic, anti-inflammatory properties and is also considered a metabolic hormone which influences the glucose and lipid metabolism. The aim of the study is to study the significance of serum adiponectin [HMW] and serum leptin and its correlation with the Lipid profile and the study of atherogenic index [AI] in the first-degree relatives [FDR] of diabetic family [DF] and non-diabetic family [nDF]. Materials & Methods: Present study is a cross-sectional analytical study conducted on 100 first-degree relatives [FDR] of both diabetic and non-diabetic families, along with their parents 50 type 2 diabetic patients and 50 non-diabetic patients. We have categorized the above study participants as groups with a and b as the diabetic and non-diabetic parents and a1 & b1 as the FDR of diabetic [DF] and non-diabetic family [nDF]. Fasting lipid profile, serum adiponectin [HMW] & serum leptin were analysed in all four groups. Result: Serum adiponectin is found significant with serum triglycerides, serum low-density lipoprotein [LDL], Leptin/adiponectin ratio and Atherogenic index [AI] between a & b and a1 & b1 groups. Conclusion: The serum adiponectin is correlated with serum Total cholesterol, TGL, LDL, Leptin/adiponectin ratio and atherogenic index mainly in the a1 first-degree relatives [FDR] of positive diabetic family history, which can be considered as the biomarker for the future risk of diabetic dyslipidaemia.

Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics

BackgroundFirst-degree relatives of type 2 diabetics (FDR) exhibit a high risk of developing type 2 diabetes (T2D) and feature subcutaneous adipocyte hypertrophy, independent of obesity. In FDR, adipose cell abnormalities contribute to early insulin-resistance and are determined by adipocyte precursor cells (APCs) early senescence and impaired recruitment into the adipogenic pathway. Epigenetic mechanisms signal adipocyte differentiation, leading us to hypothesize that abnormal epigenetic modifications cause adipocyte dysfunction and enhance T2D risk. To test this hypothesis, we examined the genome-wide histone profile in APCs from the subcutaneous adipose tissue of healthy FDR.ResultsSequencing-data analysis revealed 2644 regions differentially enriched in lysine 4 tri-methylated H3-histone (H3K4me3) in FDR compared to controls (CTRL) with significant enrichment in mitochondrial-related genes. These included TFAM, which regulates mitochondrial DNA (mtDNA) content and stability. In FDR APCs, a significant reduction in H3K4me3 abundance at the TFAM promoter was accompanied by a reduction in TFAM mRNA and protein levels. FDR APCs also exhibited reduced mtDNA content and mitochondrial-genome transcription. In parallel, FDR APCs exhibited impaired differentiation and TFAM induction during adipogenesis. In CTRL APCs, TFAM-siRNA reduced mtDNA content, mitochondrial transcription and adipocyte differentiation in parallel with upregulation of the CDKN1A and ZMAT3 senescence genes. Furthermore, TFAM-siRNA significantly expanded hydrogen peroxide (H2O2)-induced senescence, while H2O2 did not affect TFAM expression.ConclusionsHistone modifications regulate APCs ability to differentiate in mature cells, at least in part by modulating TFAM expression and affecting mitochondrial function. Reduced H3K4me3 enrichment at the TFAM promoter renders human APCs senescent and dysfunctional, increasing T2D risk.Graphical abstract

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients

BackgroundLeptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. MethodsAge, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19–39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. ResultsOf 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 μIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. ConclusionThe FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Prevalence of Prediabetes in First Degree Relatives of Patients with Type 2 Diabetes Mellitus in a Tertiary Centre in Southern Nigeria

<i>Introduction:</i> Prediabetes confers about a sixfold increased risk of diabetes and a two to threefold increased risk of cardiovascular events. A family history of diabetes is a major risk factor for the development of diabetes. The detection of prediabetes in its early stages in persons at risk could lead to the delay or prevention of the disease and subsequent adverse sequalae. <i>Methods:</i> A total of 180 first-degree relatives (FDR) of patients with type 2 diabetes and 90 controls were assessed. A fasting venous blood sample was collected for fasting plasma glucose. Following 75g of anhydrous glucose ingestion, the 2-hour post glucose load and glycated haemoglobin was assessed. Statistical significance was set at a p value <0.05. <i>Results:</i> The mean age of the cases who were first degree relatives of type 2 DM was 38.2±12.3 years with a female to male ratio of 1.4:1. The prevalence of prediabetes was 23.9% which was significantly higher than in the controls (10%; χ²=8.385, p=0.015). Using the various indices of glycaemic control, impaired fasting glucose, impaired glucose tolerance and elevated HbA1c in the FDR’s was found in 15.0%, 12.2% and 15.6% respectively. <i>Conclusion:</i> Relatives of Type 2 DM patients should be considered as primary target for diabetes preventive programs as this will necessitate institution of effective measures early to delay or prevent the onset of type 2 diabetes mellitus.

Endothelial dysfunction due to decreased nitric oxide bioavailability in dysglycaemic subjects and first-degree relatives of type 2 diabetic patients

Abstract Background/Introduction Oxidative stress plays an important role in the pathogenesis of type 2 diabetes mellitus. Purpose We aimed to investigate oxidative stress and nitrites/nitrates concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDR) of type 2 diabetic patients with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). Methods Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm (Microscan, Glycocheck), a marker of endothelial glycocalyx integrity, coronary flow reserve (CFR) in the distal left anterior descending coronary artery, left ventricular global longitudinal strain (GLS), malondialdehyde (MDA), protein carbonyls (PC) and nitrites/nitrates plasma levels were assessed at 0 and 120 min of a 2-hour OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI). Results In all subjects, there were no significant changes in MDA and PC at 120 min after OGTT (p&amp;gt;0.05). Compared with normoglycaemic subjects, in FDR and dysglycaemic subjects, nitrites/nitrates levels were significantly decreased at 120 min (−24% versus −30% versus −3%, respectively) with a parallel increase in PBR (+7% versus +10% versus −3%) and a reduction in CFR (−11% versus −14% versus −6%) and GLS (−4% versus −4% versus +0.1%) (p&amp;lt;0.05 for all comparisons). The percent reduction of nitrites/nitrates levels was associated with abnormal values of Matsuda and ISI, reversely related with the percent increase of PBR (r=−0.60, p=0.001) and positively related with the percent decrease of CFR (r=0.39, p=0.038) and GLS (r=0.48, p=0.008). Conclusion Insulin resistance determines acute endothelial responses during OGTT leading to reduced nitric oxide production with resultant coronary and myocardial dysfunction in FDR and dysglycaemic subjects. Funding Acknowledgement Type of funding sources: None.

IPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion

BackgroundThe genetic factors associated with insulin resistance (IR) are not well understood. Clinical studies on first-degree relatives of type 2 diabetic (T2D) patients, which have the highest genetic predisposition to T2D, have given insights into the role of IR in T2D pathogenesis. Induced pluripotent stem cells (iPSCs) are excellent tools for disease modeling as they can retain the genetic imprint of the disease. Therefore, in this study, we aimed to investigate the genetic perturbations associated with insulin resistance (IR) in the offspring of T2D parents using patient-specific iPSCs.MethodsWe generated iPSCs from IR individuals (IR-iPSCs) that were offspring of T2D parents as well as from insulin-sensitive (IS-iPSCs) individuals. We then performed transcriptomics to identify key dysregulated gene networks in the IR-iPSCs in comparison to IS-iPSCs and functionally validated them.ResultsTranscriptomics on IR-iPSCs revealed dysregulated gene networks and biological processes indicating that they carry the genetic defects associated with IR that may lead to T2D. The IR-iPSCs had increased lactate secretion and a higher phosphorylation of AKT upon stimulation with insulin. IR-iPSCs have increased cellular oxidative stress indicated by a high production of reactive oxygen species and higher susceptibility to H2O2 -induced apoptosis.ConclusionsIR-iPSCs generated from offspring of diabetic patients confirm that oxidative stress and increased lactate secretion, associated with IR, are inherited in this population, and may place them at a high risk of T2D. Overall, our IR-iPSC model can be employed for T2D modeling and drug screening studies that target genetic perturbations associated with IR in individuals with a high risk for T2D.

Evaluation of progression in metabolic parameters along with markers of subclinical inflammation and atherosclerosis among normoglycemic first degree relatives of type 2 diabetes mellitus patients

Evaluation of progression in metabolic parameters along with markers of subclinical inflammation and atherosclerosis among normoglycemic first degree relatives of type 2 diabetes mellitus patients

Endothelial Dysfunction Is Associated with Decreased Nitric Oxide Bioavailability in Dysglycaemic Subjects and First-Degree Relatives of Type 2 Diabetic Patients.

Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.

Serum Orosomucoid Is Associated with Serum Adiponectin, Adipose Tissue Insulin Resistance Index, and a Family History of Type 2 Diabetes in Young Normal Weight Japanese Women.

Introduction Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. Results Orosomucoid was higher in women with positive (n = 57) compared to women with negative FHD and was associated positively with FHD (both p = 0.01). Orosomucoid also showed positive associations with fasting glucose (p < 0.001), free fatty acids (p = 0.001), and HbA1c (p = 0.007), whereas there was no association with fasting insulin and serum lipids. In addition, orosomucoid was associated inversely with adiponectin (p = 0.02) and positively with adipose tissue-insulin resistance index (AT-IR, the product of fasting insulin and free fatty acids; p = 0.001) but not with homeostasis model assessment-insulin resistance, leptin, and high-sensitivity C-reactive protein. In multivariate analyses, AT-IR (standardized β, 0.22; p = 0.003), serum adiponectin (standardized β, -0.163; p = 0.032), FHD+ (standardized β, 0.178; p = 0.029), and HbA1c (standardized β, 0.213; p = 0.005) emerged as independent determinants of orosomucoid and explained 15.2% of its variability. Conclusions These results are the first to demonstrate that orosomucoid is associated not only with adipose tissue-insulin resistance and adiponectin but also with FHD.

Ten years follow up of first degree relatives of type 1 diabetes patients: presence of autoimmune biomarkers and the progression to diabetes in a retrospective cohort.

The aim of the study was to assess the autoimmunity in first degrees relatives (FDR) of patients with type 1 diabetes (T1DM) and the progression to T1DM after 10 years of follow up in the Brazilian population. Non-diabetic FDR of T1DM patients were interviewed and blood was drawn for autoantibodies measurement (GADA, IA-2A, IAA, ZnT8A). Serum samples were analyzed by standard radioligand binding assays performed at the Federal University of Rio de Janeiro (GADA, IAA and IA2A), and at the Skäne University Hospital, Sweden (ZnT8A). The FDR were interviewed by phone after 10 years to determine if they had developed T1DM. Descriptive statistical analysis was performed and results were described as means and standard deviation (SD). 81 individuals were analyzed. Thirteen subjects had positive autoantibodies associated with T1DM.10 were positive for 1 autoantibody and 3 subjects were positive for multiple autoantibodies (1 of them showed positivity for 2 autoantibodies - GADA, ZnT8A - and the other two were positive for 3 autoantibodies - GADA, IA2A, ZnT8A). The 3 subjects with multiple positive autoantibodies developed T1DM within 10 years. In Brazilian FDR of T1DM patients, the positivity for multiple autoantibodies indicate a greater chance of progression to T1DM, similar to observed in Caucasians. ZnT8A was helpful in the risk assessment for T1DM development.

Impact of triglycerides and waist circumference on insulin resistance and \u03b2-cell function in non-diabetic first-degree relatives of type 2 diabetes

BackgroundAlthough there is abundant evidence indicating the relative contribution of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-β) among first-degree relatives (FDRs) of Type 2 DM patients, few studies reported the association between HOMA-IR and HOMA-β with metabolic syndrome. Our objective was to evaluate the impact of metabolic syndrome factors on HOMA-IR, HOMA-β and glycoproteins in non-diabetic FDRs.MethodsIn this study, 103 Yemeni male subjects aged 25–42 years, with BMI < 25 kg/m2 were examined, 39 of whom were normal subjects with no family history of diabetes served as control and 64 subjects were non-diabetic FDRs of Type 2 DM patients.ResultsBoth glycoproteins, glycated haemoglobin (HbA1c) and fructosamine as well as insulin, HOMA-IR and HOMA-β were significantly (p = 4.9 × 10−9; 6.0 × 10−8; 6.6 × 10−12; 1.3 × 10−7; 5.5 × 10−12, respectively) higher in non-diabetic FDRs as compared to control group. Fasting plasma glucose, though within normal range, were significantly (p = 0.026) higher in non-diabetic FDRs. Linear regression analysis showed that both TG and WC are the main metabolic syndrome factors that significantly increased HOMA-IR (B = 0.334, p = 1.97 × 10−6; B = 0.024, p = 1.05 × 10−5), HOMA-β (B = 16.8, p = 6.8 × 10−5; B = 0.95, p = 0.004), insulin (B = 16.5, p = 1.2 × 10−6; B = 1.19, p = 8.3 × 10−6) and HbA1c (B = 0.001, p = 0.034; B = 0.007, p = 0.037).ConclusionTriglyceride and WC are the important metabolic syndrome factors associated with insulin resistance, basal β-cell function and insulin levels in non-diabetic FDR men of Type 2 DM patients. Moreover, FDRs showed insulin resistance with compensatory β-cell function (hyperinsulinaemia) suggesting that insulin resistance precede the development of pancreatic β-cell dysfunction in individuals at risk of Type 2 DM.

Adipocyte precursor cells from first degree relatives of type 2 diabetic patients feature changes in hsa-mir-23a-5p, -193a-5p, and -193b-5p and insulin-like growth factor 2 expression.

First-degree relatives (FDRs) of type 2 diabetics (T2D) feature dysfunction of subcutaneous adipose tissue (SAT) long before T2D onset. miRNAs have a role in adipocyte precursor cells (APC) differentiation and in adipocyte identity. Thus, impaired miRNA expression may contribute to SAT dysfunction in FDRs. In the present work, we have explored changes in miRNA expression associated with T2D family history which may affect gene expression in SAT APCs from FDRs. Small RNA-seq was performed in APCs from healthy FDRs and matched controls and omics data were validated by qPCR. Integrative analyses of APC miRNome and transcriptome from FDRs revealed down-regulated hsa-miR-23a-5p, -193a-5p and -193b-5p accompanied by up-regulated Insulin-like Growth Factor 2 (IGF2) gene which proved to be their direct target. The expression changes in these marks were associated with SAT adipocyte hypertrophy in FDRs. APCs from FDRs further demonstrated reduced capability to differentiate into adipocytes. Treatment with IGF2 protein decreased APC adipogenesis, while over-expression of hsa-miR-23a-5p, -193a-5p and -193b-5p enhanced adipogenesis by IGF2 targeting. Indeed, IGF2 increased the Wnt Family Member 10B gene expression in APCs. Down-regulation of the three miRNAs and IGF2 up-regulation was also observed in Peripheral Blood Leukocytes (PBLs) from FDRs. In conclusion, APCs from FDRs feature a specific miRNA/gene profile, which associates with SAT adipocyte hypertrophy and appears to contribute to impaired adipogenesis. PBL detection of this profile may help in identifying adipocyte hypertrophy in individuals at high risk of T2D.

Association of c-reactive protein and lipid accumulation product with fasting insulin levels in obese first degree relatives of type-2 diabetics

The obese first degree relatives of type 2 diabetics are more prone to develop diabetes mellitus in later life. Having one parent with type 2 diabetes mellitus carries 1.6 fold and both the parents with type 2 diabetes mellitus (T2DM) has 3.2 fold higher risk of developing T2DM. Lipid accumulation product (LAP) is a simple and reliable index of central lipid accumulation. It combines waist circumference and triacyglycerols. Studies have revealed that LAP is a better indicator than Body mass index (BMI) in predicting risk of diabetes mellitus and metabolic syndrome. Weight gain and body mass are the main factors in increasing risk for diabetes mellitus. Fat cells produce chemicals (inflammatory markers) that cause inflammation. Internal inflammation can also leads to the development of diabetes mellitus. C - reactive protein (CRP) is an inflammatory marker produced by liver cells. Studies have shown that elevated CRP is linked to higher risk of developing diabetes in later life. In this study, we have found an association of Serum Insulin (SI), LAP and CRP in first degree relatives of type-2 diabetics. We had taken 100 Obese first degree relatives of type-2 diabetics as subjects and 100 age and sex matched first degree relative of T2DM without obesity were taken as controls. Fasting blood glucose, Fasting TGs estimations were done using fully autoanalyser. Waist circumference (in cm) was measured and also LAP score was calculated by using the formula, i.e. (WC-58)*TG mmol/l &amp; (WC-65)*TG mmol/l in females and males respectively. CRP was estimated using Nyco-card reader. Serum Insulin was measured using ELISA reader. The Mean ±SD of Serum Insulin, CRP, LAP, FBS in Group I were found to be 15.9±2.54, 6.05±1.5mg%, 106.8±40.7, 133.0±18.9 mg% respectively compared to Group II 9.2±1.28, 2.59±1.2, 25.7±14.6, 78.7±8.2. A highly significant correlation of LAP and CRP (p&amp;#60;0.01) was found in study group. A significant correlation of Serum Insulin (SI), CRP and LAP score (p&amp;#60;0.5) was found. This study suggested that first degree relatives of type-2 diabetics should have some modification in their lifestyle as they are at increased risk of metabolic syndrome, diabetes and coronary artery disease.

Influence of Metabolic Syndrome on Vibration Perception Threshold in First-Degree Relatives of Type 2 Diabetes Mellitus

Objectives: To investigate influence of metabolic syndrome on vibration perception threshold in first-degree relatives of type 2 diabetes who were not diagnosed with diabets before. Material and Methods: First-degree relatives of type 2 diabetes at the age of 40 - 60 s who had not been diagnosed with diabetes before were enrolled. Height, weight, waist circumference, hip circumference, blood pressure (systolic and diastolic blood pressure), body fat percentage, fasting plasma lipid, fasting plasma glucose, 2-hour blood glucose after 75 g oral glucose and vibration perception threshold were measured. Results: 58 subjects were diagnosed with the level of vibration perception threshold ≥ 16 V. Vibration perception threshold in the metabolic syndrome group was significantly higher than that in the non-metabolic syndrome group (P p P < 0.05). Vibration perception threshold was positively correlated with weight, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose and 2-hour blood glucose. Stepwise multiple regression analysis showed that there was a positive correlation between waist circumference, systolic blood pressure and vibration perception threshold. Conclusion: Some first-degree relatives of type 2 diabetes who have not been diagnosed with diabetes have high risk of peripheral neuropathy, especially those with metabolic syndrome. Waist circumference and blood pressure are the main factors affecting Vibration perception threshold levels. Early detection of vibration perception threshold should be performed in first-degree relatives of type 2 diabetes with metabolic syndrome. Waist circumference and blood pressure may be important risk factors of peripheral neuropathy for them.

Patterns of changes in fasting plasma glucose, hemoglobin A1c and the area under the curve during oral glucose tolerance tests in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

This study aimed to identify the patterns of changes in glycemic indices over time in prediabetics and to classify these subjects as either having a high or low risk for developing diabetes in future. This prospective 16-year cohort study was conducted among 1228 prediabetic subjects. Three measurements including first visit, mean values during the follow-up period, and last visit from fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), and area under the curve during an oral glucose tolerance test (OGTT AUC) were used to evaluate the patterns of changes by using the latent Markov model (LMM). The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The LMM identified 2 latent states of subjects in terms of changes in FPG, HbA1c, OGTT AUC, and the combination of these glycemic measures: a low tendency to progress diabetes and a high tendency to progress diabetes with the latent state sizes (87, 13%), (94, 6%), (57, 43%), and (84, 16%), respectively. The LMM showed that the probability of transitioning from a low tendency to a high tendency to progress diabetes was higher than the probability of transitioning in the opposite direction. Based on a long-term evaluation of patterns of changes in glycemic indices, we classified prediabetic subjects into 2 groups (high or low risk to progress diabetes states in future). Also, the method used enabled us to estimate the transition probabilities from low- to high-risk states and vice versa. Our results reemphasized the values of all 3 glycemic measures in clinical settings for identifying prediabetic people with a high risk of progressing diabetes and the need for more effective prevention strategies, which should be conducted as urgently in prediabetic life as high-risk subjects.

Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients

BackgroundLipid abnormality pervasively is associated with the risk of type 2 diabetes mellitus. To the best of our knowledge, there is no study that has examined the longitudinal changes in a wide range of serum lipid profiles in prediabetic subjects in association with the risk of developing type 2 diabetes mellitus in the future. This study aimed to identify the patterns of changes in lipid profiles over time in prediabetic patients and to classify these subjects in order to highlight which patients are at high risk for future diabetes.MethodsThis prospective 16-year (2003–2019) cohort study was conducted among 1228 prediabetic subjects. The study subjects were followed, and the changes in their lipid profiles, including triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were evaluated. The latent Markov model was used for data analysis.ResultsThe mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The latent Markov model identified two latent states of subjects in terms of changes in lipid profiles: a low tendency to progress diabetes / high tendency to progress diabetes (74, 26%). The latent Markov model showed that the transition probability from a “low tendency to progress diabetic” state to a “high tendency to progress diabetic” state was lower than the transition probability from “high tendency to progress diabetic” state to “low tendency to progress diabetic” state.ConclusionsThe present study showed that more than half of the first-degree relatives of T2DM had approximately normal lipid profiles and that these patients are more inclined to transition from a higher- to a lower-tendency diabetic state. These findings confirm the value of regular screening of first-degree relatives of T2DM. Moreover, preventive intervention strategies are recommended to reduce their risk of developing T2DM.

Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients: A 15-year prospective cohort study.

BACKGROUNDType 2 diabetes mellitus (T2DM) has high morbidity and mortality worldwide, therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness. A strong correlation between severity of metabolic syndrome (MetS) and HbA1c, fasting insulin and insulin resistance has been reported. Accordingly, the MetS severity score (or MestS Z-score) can potentially be used to predict the risk of T2DM progression over time.AIMTo evaluate the association the of MestS Z-score in first degree relatives (FDRs) of T2DM with the risk of prediabetes and type 2 diabetes in future.METHODSA prospective open cohort study was conducted between 2003-2018. At baseline, the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance test. Relative risk (RR) and 95% confidence interval were calculated based on logistic regression. The receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR population.RESULTSBaseline MetS Z-scores were associated with the its latest values (P < 0.0001). Compared with individuals who were T2DM free at the end of follow up, those who developed T2DM had higher MetS Z-score at baseline (P < 0.001). In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline, the RR for developing future T2DM and prediabetes was (RR = 1.94, RR = 3.84), (RR = 1.5, RR = 2.17) in total population and female group, respectively (P < 0.05). The associations remained significant after adjusting the potential confounding variables. A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population, respectively.CONCLUSIONThe MetS Z-score was associated with an increased risk of future T2DM. Appropriate interventions at earlier stages for preventing and attenuating MetS effects may be considered as an effective strategy for FDR as at-risk population.

Prevalence of NAFLD and Its Association with Insulin Resistance in First Degree Relatives of Type 2 Diabetes

Prevalence of NAFLD and Its Association with Insulin Resistance in First Degree Relatives of Type 2 Diabetes

Association of gamma glutamyl transferase activity with fasting glucose among first degree relatives of type 2 diabetes patients

Association of gamma glutamyl transferase activity with fasting glucose among first degree relatives of type 2 diabetes patients - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.096, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res