Impaired Fasting Glucose Patients Research Articles

Impaired fasting glucose is associated with lower glomerular filtration rate decline among men but not women –a large cohort study from Israel

ObjectivesEarly stages of diabetes are associated with an increased glomerular filtration rate (GFR). Little is known, however, about the change in GFR among patients with impaired fasting glucose (IFG). We aimed to evaluate the yearly decline rate of GFR among IFG patients. MethodsA retrospective analysis of a large cohort of subjects attending a medical screening center in Israel. Patients with diabetes mellitus and patients with decreased estimated GFR (eGFR) were excluded. We divided the cohort into 2 subgroups; Healthy controls and impaired fasting control subjects. For each group, we calculated the average yearly estimated GFR decline (ΔeGFR). The results were adjusted for age, BMI, hypertension and smoking status. Results8176 subjects met the inclusion criteria. The median follow up time was 4.8 years (range 2.0 to 13.4). For the whole cohort (men and women), yearly ΔeGFR was −0.68 among healthy controls, and − 0.47 among IFG patients (p = .003). Among men, average yearly ΔeGFR in healthy controls and IFG patients was −0.7 and − 0.4, respectively (p = .0002). All results remained significant after adjusting for age, BMI, hypertension, smoking status and level of HDL and triglycerides. In contrast, among IFG women there was no significant difference in ΔeGFR in comparison with healthy women. ConclusionsImpaired fasting glucose is associated with a decreased rate of GFR reduction compared with healthy subjects. This effect is gender dependent - observed in men but not in women. A mechanism of glomerular hyperfiltration might be involved.

Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: effect of extra-virgin olive oil.

Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG). This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120min after lunch. In patients not given EVOO oxidative stress as assessed by sNox2-dp and oxLDL significantly increased at 60 and 120min concomitantly with an increase of LPS and Apo-B48. In these patients, changes of LPS were correlated with Apo-B48 (Rs = 0.542, p = 0.002) and oxLDL (Rs = 0.463, p = 0.010). At 120min, LPS (β - 15.73, p < 0.001), Apo-B48 (β - 0.14, p = 0.004), sNox2-dp (β - 5.47, p = 0.030), and oxLDL (β - 42.80, p < 0.001) significantly differed between the two treatment groups. An inverse correlation was detected between polyphenols and oxLDL (R - 0.474, p < 0.005). In vitro study showed that LPS, at the same concentrations found in the human circulation, up-regulated Nox2-derived oxidative stress via interaction with Toll-like receptor 4. Post-prandial phase is characterized by an oxidative stress-related inflammation potentially triggered by LPS, a phenomenon mitigated by EVOO administration.

Reduced mitochondrial DNA content in lymphocytes is associated with insulin resistance and inflammation in patients with impaired fasting glucose.

Altered mitochondrial DNA (mtDNA) is the most common denominator to numerous metabolic diseases. The present study sought to investigate the correlation between mtDNA content in lymphocytes and associated clinical risk factors for impaired fasting glucose (IFG). We included 23 healthy control and 42 IFG participants in this cross-sectional study. The measurements of mtDNA content in lymphocytes and pro-inflammatory markers derived from both normal and diseased individuals were quantified. Spearman partial correlation and multivariate statistical analyses were employed to evaluate the association between mtDNA content and other metabolic covariates in IFG. Reduced mtDNA content was observed in the IFG group with microvascular complications than those without complications. The IFG patients with lowest median of mtDNA content had considerably elevated hyperglycemia, insulin resistance and inflammation. The adjusted partial correlation analysis showed that mtDNA content was positively correlated with HDL-cholesterol and IL-10 (P < 0.005 for all). Further, multiple linear regression analyses verified that reduced mtDNA content in lymphocytes was independently associated with HOMA-IR (β = 0.027, P = 0.003), HbA1c (β = 0.652, P = 0.002), HDL-cholesterol (β = - 1.056, P = 0.021), IL-6 (β = 0.423, P = 0.002), IL-10 (β = - 1.234, P = 0.043) and TNF-α (β = 0.542, P < 0.001) after adjustment for confounding factors. Our data show that reduced mtDNA content in lymphocytes was associated with insulin resistance and inflammation in individuals with IFG.

The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

BACKGROUNDPrediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear.OBJECTIVESThe purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders.DESIGNRetrospective study.SETTINGHealth Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010–2014.PATIENTS AND METHODSParticipants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded.MAIN OUTCOME MEASURESCorrelation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories.RESULTSOf 1112 participants, 346 (34.2%) had a CAC score >0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P<.001) and in Kruskal-Wallis test the mean CAC score differed by FPG group (P<.001). After adjustment for other factors in a multiple logistic regression analysis, those subjects with FPG ≥110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110≤FPG [mg/dL] <120, OR=2.507, P=.002; 120≤FPG [mg/dL] <126, OR=3.568, P=.001 vs. <100 mg/dL)CONCLUSIONIFG (especially FPG≥110 mg/dL) could be an independent risk factor for CAC. These associations were not altered after adjustment for other possible confounders.LIMITATIONSPossible misclassification because data taken from a single blood test. No HbA1c tests or repeated FPG tests. No adjustment for other potentially important confounders.

Fasting glycaemia is a predictor of outcome after acute myocardial infarction

Background: Patients with recent myocardial infarction have an increased incidence of impaired fasting glucose (IFG) and new-onset diabetes. There is a clear relationship between elevated fasting glucose during acute myocardial infarction and increased mortality and morbidity risk. Objective: To find out the impact of fasting glycaemia as a predictor of outcome of patients with acute myocardial infarction. Methods: A total of 102 patients with acute myocardial infarction of first attack were selected according to inclusion and exclusion criteria. Fifty-one patients with acute myocardial infarc­tion having fasting hyperglycaemia were enrolled as case group and another 51 patients with acute myocardial infarctions having fasting euglycaemia were enrolled as control group. Results: Among the diabetic patients, acute left ventricular failure (ALVF) developed in 22 (68.8% ), arrhythmias in 5 (16.6%) and cardiovascular mortality in 8 (25.0% ) patients ; it was 7 (36.8%), 4 (21.1 %) and 4 (21.1 %) respectively in IFG patients; and 7 (13.7%) ,4 (7.8%) and 2 (3.9%) respec­tively in euglycaemia patients. Acute left ventricular failme and 30 days CV mortality significantly differed among the groups (p&lt;0.001 and p=0.015 respectively). But no significant difference in arrhythmias (p=-0.284). Conclusions: The patients of impaired fasting glucose (IFG) and diabetes mellitus both were predictor for in hospital heart failure (ALVF) and 30-day cardiovascular mortality as compared to euglycaemia.

Severe dyslipidemia and immune activation in HIV patients with dysglycemia

Background and Objective: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood.Methods: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels ≥126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101–125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry.Results: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low-density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders.Conclusion: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders.

Extra virgin olive oil improves post-prandial glycemic and lipid profile in patients with impaired fasting glucose

Extra virgin olive oil (EVOO) improves post-prandial glycaemia in healthy subjects but it has never been investigated if this can be detected in pre-diabetic patients. We investigated if EVOO affects post-prandial glucose and lipid profile in patients with impaired fasting glucose (IFG). Thirty IFG patients were randomly allocated to a meal containing or not 10g of EVOO in a cross-over design. Before, 60min and 120min after lunch a blood sample was taken to measure glucose, insulin, Glucagon-like peptide-1 (GLP1), dipeptidyl-peptidase-4 (DPP4) activity, triglycerides (TG), total cholesterol, HDL-cholesterol and Apo B-48. The meal containing EVOO was associated with a reduction of glucose (p=0.009) and DPP4 activity (p<0.001) and a significant increase of insulin (p<0.001) and GLP-1 (p<0.001) compared with the meal without EVOO. Furthermore, the meal containing EVOO showed a significant decrease of triglycerides (p=0.002) and Apo B-48 (p=0.002) compared with the meal without EVOO. Total cholesterol and HDL cholesterol levels did not significantly change between the two groups. This is the first study to show that in IFG patients EVOO improves post-prandial glucose and lipid profile with a mechanism probably related to incretin up-regulation.

Capsule Commentary on Castro et al., Statin Use, Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients.

Capsule Commentary on Castro et al., Statin Use, Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients.

Association between the Levels of IL-6, sE-Selectin and Distal Sensory Nerve Conduction Studies in Patients with Prediabetes

Aim: To determine the association between interleukin-6 (IL-6) and soluble E-selectin (sE-selectin) levels with the electrodiagnostic abnormalities in patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Methods: Serum HbA1c, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, IL-6 and sE-selectin levels were analyzed in 25 IFG patients, 22 IGT patients and 41 controls. Nerve conduction studies (NCS) of sural, dorsal sural (DS), medial dorsal cutaneous and medial plantar sensory nerves were conducted. Results: HbA1c and IL-6 levels were significantly higher in IFG and IGT patients than the controls. IGT patients had higher sE-selectin levels compared to controls and IFG patients. IL-6 levels were significantly correlated with levels of CRP, fibrinogen, ESR and sE-selectin in patients with prediabetes. Both IFG and IGT patients had substantial impairments in very distal sensory NCS. IL-6 levels were positively correlated with HbA1c and negatively correlated with DS NCS in prediabetic patients. Conclusions: Inflammation and endothelial dysfunction might be important in patients with IFG or IGT. Furthermore, our findings strengthen the idea that inflammation (increased levels of IL-6) might be associated with early electrophysiological impairments in patients with prediabetes. NCS of the most distal sensory nerves significantly enhanced the diagnosis of subclinical neuropathy in patients with prediabetes. Subclinical peripheral sensory neuropathy should be investigated in prediabetes to lower the number of future outcomes they are associated with.

Statin Use, Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients.

The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk. We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG). Observational cohort study of 13,508 normoglycemic patients (n = 4460; 33% taking statins) and 4563 IFG patients (n = 1865; 41% taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999-2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan-Meier method. The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality. After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95% CI, 1.05 to 1.35; p = 0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p = 0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95% CI, 0.66 to 0.80; p < 0.0001) and IFG patients (HR 0.77, 95% CI, 0.64 to 0.91; p = 0.0029) with statin use. In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19-24%) risk.

동기강화면담이 공복혈당장애 환자의 건강증진생활양식, 행동변화단계, 당화혈색소값에 미치는 효과

The purpose of this study was to develop a motivational enhancement therapy(MET) for impaired fasting glucose(IFG) patients in early stages of health behavior change and evaluate its effects on health promotion lifestyle, the stages of change and HbAlc. Data was collected in Health Center of U city, December 2011 to March 2012, conducted on 78 IFG patients who visited to the Health center, they randomized to intervention group(n=27) and control group(n=33). The intervention group received the MET, the control group received standard care. This MET programe was applied from MET programe. After developing, it confirmed content validity. Data was analyzed using descriptive statistics, and t-test with the SPSS WIN 20.0 program. Participants in the intervention group reported significantly increased scores of the stage of change(t=-20.224, p=.000) compared to those of the control group but no difference of health behaviors(t=-1.297, p=.200) and HbAlc(t=.794, p=.431). The findings indicate that the MET is an effective intervention in improving ealth behaviors and expect to be applied effectively to the preparation for implementation of health care interventions.

Identification of Risk Factors Affecting Impaired Fasting Glucose and Diabetes in Adult Patients from Northeast China.

Background: Besides genetic factors, the occurrence of diabetes is influenced by lifestyles and environmental factors as well as trace elements in diet materials. Subjects with impaired fasting glucose (IFG) have an increased risk of developing diabetes mellitus (DM). This study aimed to explore risk factors affecting IFG and diabetes in patients from Northeast China. Methods: A population-based, cross-sectional survey of chronic diseases and related risk factors was conducted in Jilin Province of Northeast China. All adult residents, aged 18–79, were invited to participate in this survey using the method of multistage stratified random cluster sampling. One hundred thirty-four patients with IFG or DM and 391 healthy control subjects were recruited. We compared demographic factors, body size measurements, healthy-related behaviors, and hair metallic element contents between IFG/diabetes patients and healthy individuals. Results: IFG/diabetes patients had a greater weight, waist, hip, and body mass index (BMI) than control subjects. Significant differences in the content of zinc (Zn), potassium (K), copper (Ca), and sodium (Na) as well as Cu/Zn ratios between IFG or DM patients and control subjects (p < 0.05) were also observed. Hair Cu, selenium (Se), and Na contents were positively correlated with blood glucose levels (Cu: rs = 0.135, p = 0.002; Se: rs = 0.110, p = 0.012; Na: rs = 0.091, p = 0.038). Polytomous logistic regression adjusting for age, sex, family history of diabetes and BMI, showed that subjects with high BMI were more likely to develop IFG and DM (IFG: OR = 1.15, OR 95% CI = 1.02–1.29; DM: OR = 1.15, OR 95% CI = 1.01–1.33). Moreover, rarely or never eating fruits was a risk factor for DM (OR = 5.46, OR 95% CI = 1.87–15.98) but not for IFG (OR = 1.70, OR 95% CI = 0.72–4.02). Subjects with abdominal obesity or DM history were more susceptible to DM (abdominal obesity: OR = 2.99, OR 95% CI = 1.07–8.37; DM history: OR = 2.69, OR 95% CI = 1.01–7.20). We found that subjects living in Changling County had a significantly lower chance to suffer from IFG (OR and 95% CI for OR: 0.25, 0.08–0.74). Men and 60–69 years old subjects were at increased risk for IFG (male: OR = 3.51, OR 95% CI = 1.34–9.18; age 60–69: OR = 6.64, OR 95% CI = 1.36–32.47). We did not find significant associations of IFG or DM with certain lifestyles (such as eating more meat, exercise or physical activity, smoking, or alcohol drinking) or the content of some metallic elements (such as iron (Fe), Zn , K, calcium (Ca), Na, or magnesium (Mg)). Conclusions: This study demonstrated that less or no fruit eating, DM family history, abdominal obesity conferred vulnerability to DM. Living in Changling County, men and 60–69 years old subjects were found to be risk factors for IFG. Subjects with high BMI were more likely to develop IFG and DM.

Visceral fat is better related to impaired glucose metabolism than body mass index after kidney transplantation.

The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P < 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.

The profile of hypertension and dyslipidemia in prediabetic subjects; results of the Isfahan Diabetes Prevention program: A large population-based study.

Background:The present study was designed to evaluate hypertension and dyslipidemia in prediabetic subjects with a family history of type 2 diabetes (first-degree relatives), and they were compared with the normal glucose-tolerance subjects.Materials and Methods:Three thousand and eighty-six (788 men and 2298 women) subjects were selected from a consecutive sample of patients with Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), and Combined (IFG and IGT), and their first-degree relatives formed the control group. Potential risk factors for diabetes including age, gender, body size, HbA1c, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, blood pressure (BP), urine microalbumin, and family and personal medical history were assessed.Results:The studied participants included 300 IGT patients (9.7%), 625 IFG patients (44.9%), 411 combined patients (13.3%), and 1750 (56.7%) normal subjects. Aging led to increase in hypertension. Increase in body mass index (BMI) led to an increase in the prevalence of hypertension significantly in all groups. The mean triglyceride in the normal group was different in comparison with that of the IGT (P < 0.05) and combined (P < 0.001) groups. Differences in total cholesterol were observed in the normal group when compared with the IGT (P < 0.05) and combined (P < 0.001) groups, and of the combined group in comparison with the IGT (P < 0.05) group. The difference in LDL level was related to the combined group in comparison with IGT, marginally (P < 0.1), and normal in comparison with the combined group (P < 0.05).Conclusion:Prevalence of hypertension was not significantly different between the groups, however, in prediabetic patients it was higher than in the normal group, and prevalence of dyslipidemia in prediabetic subjects was significantly higher than in the normal group.

Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus

We found that type 2 diabetes mellitus (T2DM) was associated with increased fracture risks in non-obese postmenopausal Chinese women, and suppressed bone turnover might be the underlying mechanism. This is the first study evaluating and explaining the association of T2DM with osteoporotic fracture in Chinese population with such high homogeneity. The aim of this study was to investigate the association of T2DM with osteoporotic fracture in postmenopausal Chinese women. One thousand four hundred ten postmenopausal women were included and stratified into non-obese population [body mass index (BMI) < 25 kg/m(2)] and obese population (BMI ≥ 25 kg/m(2)). Each type of population was classified into diabetes group, impaired fasting glucose (IFG) group, and normal glucose group. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum C-terminal telopeptide of type I collagen (β-CTX) and serum N-amino terminal prepeptide of type 1 procollagen (P1NP) were quantified. Vertebral fractures (VFs) and non-VFs were assessed by vertebral X-ray and questionnaire, respectively. Comparing to normal glucose group, diabetes group and IFG group both had lower levels of P1NP and β-CTX, despite population types. Despite having non-decreased BMD, non-obese diabetic patients had higher risks of total fracture and VF than BMI-matched normal glucose subjects (both P < 0.05). Non-obese population was further classified by a mean value of P1NP or β-CTX. Non-obese diabetic patients with low P1NP or high β-CTX had higher fracture risks (both P < 0.05), comparing to non-obese normal glucose subjects with high P1NP or high β-CTX, respectively. Type 2 diabetic patients had suppressed bone turnover, which might explain the increased fracture risks, independent of BMD. IFG patients might also have poor bone quality and need early prevention.

Total antioxidant status and markers of oxidative stress in subjects with normal or impaired glucose regulation (IFG, IGT) in diabetic patients

Background. We investigated the ischemia-modified albumin (IMA), advanced oxidation protein products (AOPPs), prooxidants–antioxidants balance (PAB), and ferric reducing antioxidant power (FRAP) concentrations in patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) and compared the results to those of normoglycemic individuals at baseline and 2 hours after glucose loading. Methods. An oral glucose tolerance test was performed on age-matched subjects (n = 110) with a body mass index (BMI) < 27 kg/m2. Subjects were categorized as normoglycemic (n = 35), IFG (n = 25), IGT (n = 30) and DM (n = 20) according to the WHO criteria. The IMA, AOPP, PAB, FRAP concentrations were determined by colorimetric methods. Results. At baseline, the AOPP concentrations were significantly higher in subjects with IFG and DM compared to normoglycemic subjects (p < 0.01 for all cases). The IFG, IGT and DM patients had a significantly higher IMA at baseline when compared with the normoglycemic individuals (p < 0.001 for all cases). The IMA in IFG subjects was significantly elevated (p < 0.05), while in DM patients, the IMA was significantly decreased (p < 0.001) after glucose loading with respect to baseline concentrations. Following glucose loading, the PAB was significantly decreased from baseline concentrations in normoglycemic individuals (p < 0.001) and in the IFG (p < 0.001) and IGT (p < 0.001) patients. Conclusion. In subjects with impaired glucose metabolism, the hyperglycemia is associated with increased IMA, AOPP and PAB concentrations. Increased IMA in subjects with IFG and decreased FRAP concentrations in subjects with IGT after glucose loading suggests that an increase in glucose concentrations can lead to tissue damage by increasing oxidative stress.

Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes

Background/aims. In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose. Material and methods. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated. Results. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6). Conclusion. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.

Effects of niacin on the incidence of new onset diabetes and cardiovascular events in patients with normoglycaemia and impaired fasting glucose

This post hoc analysis from the Coronary Drug Project (CDP) evaluated the effects of niacin vs. placebo on the incidence of new onset type 2 diabetes mellitus (T2DM) and cardiovascular event rates in patients with normal and impaired fasting glucose (IFG). The CDP was a randomised, placebo-controlled clinical trial of lipid-modifying agents in men with previous myocardial infarction. Normoglycaemia and IFG were defined as fasting plasma glucose (FPG) < 5.6 mmol/l and FPG ≥ 5.6 but < 7.0 mmol/l, respectively. New onset T2DM was defined by ≥ 1 of the following: clinical diagnosis of T2DM, use of an antihyperglycaemic therapy, or two FPG values ≥ 7.0 mmol/l. The incidence of new onset T2DM was higher in patients with IFG (16.5%) compared with those with normoglycaemia (5.4%), and was slightly higher with niacin vs. placebo in both normoglycaemic (6.8% vs. 4.9%; p = 0.07) and IFG (19.8% vs. 15.2%; p = 0.05) patients. Consistent with previous analyses, the cardiovascular benefit of niacin was independent of baseline glycaemic status (normal, IFG, T2DM) and change in fasting glucose level from baseline to year 1. Despite a modest increase in risk of new onset T2DM with long-term niacin therapy, there is a potential cardiovascular benefit of niacin.

Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects

BackgroundOxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 (MLH1) gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS), we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1. These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2) and impaired fasting glucose (IFG).MethodsIn this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1, MSH2, and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA) and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount.ResultsThe intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1, DNMT1, and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate.ConclusionThis vitamin and antioxidant rich diet affected the CpG methylation of MLH1. The higher methylation might be a result of the ROS scavenging antioxidant rich diet, leading to lower activity of DNA demethylating enzymes. Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances. NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms.