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Despite a growing body of research indicating a link between fasting glucose levels and mortality, the relationship between fasting glucose and all-cause and cancer mortality remains inconsistent. In this study, we used Cox regression and restricted cubic spline models to analyze the association and dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality in a retrospective cohort based on data from the 2015 health check-ups of residents in Quzhou City. After a mean follow-up of 5.31 years for 148,755 study participants, 10,345 deaths occurred, with an all-cause mortality density of 131.09/10,000 person-years, of which 2,845 were cancer deaths, with a cancer mortality density of 36.05/10,000 person-years. There was a "J" shaped dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality. Relative to normal fasting glucose (NFG), the risk of all-cause mortality (HRs and 95% CIs) in the impaired fasting glucose (IFG) and diabetes mellitus (DM) groups was 1.11 (1.06, 1.16) and 1.43 (1.35, 1.52), respectively, and the risk of cancer mortality in the DM group was 1.22 (1.09, 1.37). In this cohort study, we found that fasting plasma glucose levels were significantly associated with the risk of all-cause and cancer mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Obesity is associated with concomitant chronic conditions. An early metabolic consequence of obesity is disruption of glucose and insulin homeostasis. One of the consequences is impaired fasting glucose (IFG). Visceral fat is metabolically more harmful than subcutaneous fat, but few information is available regarding the association between the risk of abnormal glucose in increased waist circumference., Methods: This study is based on a cross sectional of 1,381 population-based from Palembang, Indonesia. The eligibility requirements subject were to be older than 18 and consent to taking fasting glucose and lipid profile tests as well as physical exams measuring their body weight, height, blood pressure, abdominal circumference, and waist circumference., Results: The number of subjects consisting of 798 noncentral obesity with normoglycemia, 376 central obesity with normoglycemia, and 207 central obesity with concomitant IFG. The prevalence central obesity with concomitant IFG was 35.51%. In subjects with central obesity, there were significant differences in proportions based on sex, age, marital status, education, and occupation. In multivariate analysis show that the risk factors that contribute to having a significant association with central obesity with concomitant IFG are sex (female), age (>40 years), blood pressure (hypertension), and HDL-C <50 mg/dL (p<0.001). The analysis also founded that there was a significant difference in the dietary pattern of sweet foods (p = 0.018), sweet drinks (p = 0.002), soft drinks (p = 0.001) and smoking habit (p<0.001) between subjects with obesity central and concomitant IFG compared to subjects with noncentral obesity. The majority of subjects with obesity central and concomitant IFG had consuming these risky foods >6 times/week., Conclusion: The prevalence of central obesity with IFG is quite high. There are significant differences in the characteristics, lipid profile, blood pressure, dietary pattern, and smoking habit of central obesity with concomitant IFG was confirmed in this population-based observational study., Competing Interests: The author declares no conflict of interest., (Copyright: © 2024 Liberty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828., Methods: We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables., Results: By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (β = -0.05 mmol/L/year per allele, p = 0.058 among women; β = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes., Conclusions: Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rivara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ramadan Intermittent Fasting (RIF) has the potential to alter hormonal levels in the body. This study investigates the impact of RIF on hormonal levels among healthy individuals during Ramadan., Methods: A systematic review and meta-analysis of previously published studies were conducted, focusing on healthy non-athlete adults. The intervention examined was Ramadan Intermittent Fasting, and the primary outcomes assessed were changes in endocrine hormonal and biochemical parameters. The pooled effect measure was expressed as odds ratio (OR) and 95% confidence interval (CI) using the random-effects model., Results: A total of 35 original articles were retrieved, with a combined sample size of 1,107 participants eligible for the meta-analysis. No significant relationship was found between pre- and post-Ramadan hormonal levels of T3, T4, TSH, FT3, FT4, Testosterone, LH, FSH, Prolactin, PTH, Calcium, and Phosphorus (P-value<0.05). However, a substantial decrease in morning cortisol levels was observed across the studies (P-value: 0.08, Hedges' g = -2.14, 95% CI: -4.54, 0.27)., Conclusions: Ramadan Intermittent Fasting results in minimal hormonal changes and is a safe practice for healthy individuals. The fasting regimen appears to disrupt the circadian rhythm, leading to a decrease in morning cortisol levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Poursalehian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare the rate and extent of absorption of a launched generic calcium dobesilate capsule versus the branded reference formulation under fasting and fed conditions in healthy Chinese subjects, and to assess their bioequivalence and tolerability., Methods: This single-dose, open-label, randomized-sequence, 2-period crossover bioequivalence study was conducted on healthy Chinese volunteers aged 18 to 45 years. Subjects received a single 0.5 g dose of calcium dobesilate capsule under fasting or fed conditions, with a 3-day washout period between doses of the test (T) and reference (R) formulations. Blood samples were collected before and up to 24 hours after administration. The plasma concentration of calcium dobesilate was determined by a validated Liquid chromatography-tandem mass spectrometry method. Non-compartmental analysis was applied to identify the pharmacokinetic (PK) properties. The primary PK parameters including the maximal plasma concentration (Cmax), the area under the plasma concentration-time curve (AUC0-t), and the AUC extrapolated to infinity (AUC0-inf) were used for bioequivalence evaluation., Results: The mean of PK parameters for T and R capsules under fasting (fed) condition were: Cmax, 13.57 (6.71) and 12.59 (7.25) μg/mL; AUC0-t, 97.32 (79.74) and 96.97 (80.71) h*μg/mL; AUC0-inf, 101.68 (88.01) and 101.64 (87.81) h*μg/mL. The 90% confidence intervals (CIs) of GMRs under fasting (fed) condition were: Cmax, 97.91%-116.62% (88.63%-96.53%); AUC0-t, 97.15%-104.00% (96.58%-101.39%); and AUC0-inf, 97.19%-102.89% (98.67%-103.99%). These 90% CIs were all within the bioequivalence range of 80%-125%. All adverse events were mild., Conclusion: In this study, the T calcium dobesilate 0.5 g capsule was bioequivalent to the reference product under both fasting and fed conditions. Taking food would slow down its rate and reduce its amount of absorption. Both formulations were generally well tolerated., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats., Competing Interests: The authors have read the journal’s policy and have the following competing interests: MN, AK, and TI are paid employees of Matsutani Chemical Industry Co., Ltd. D-Allulose is a marketed product of Matsutani Chemical Industry Co., Ltd. These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Hemolysis, icterus, and lipemia (HIL) of blood samples have been a concern in hospitals because they reflect pre-analytical processes' quality control. However, very few studies investigate the influence of patients' gender, age, and department, as well as sample-related turnaround time, on the incidence rate of HIL in fasting serum biochemistry specimens., Methods: A retrospective, descriptive study was conducted to investigate the incidence rate of HIL based on the HIL index in 501,612 fasting serum biochemistry specimens from January 2017 to May 2018 in a tertiary university hospital with 4,200 beds in Sichuan, southwest China. A subgroup analysis was conducted to evaluate the differences in the HIL incidence rate by gender, age and department of patients, and turnaround time of specimens., Results: The incidence rate of hemolysis, lipemia and icterus was 384, 53, and 612 per 10,000 specimens. The male patients had a significantly elevated incidence of hemolysis (4.13% vs. 3.54%), lipemia (0.67% vs. 0.38%), and icterus (6.95% vs. 5.43%) than female patients. Hemolysis, lipemia, and icterus incidence rate were significantly associated with the male sex with an odds ratio (OR) of 1.174 [95% confidence interval (CI), 1.140-1.208], 1.757 (95%CI: 1.623-1.903), and 1.303 (95%CI: 1.273-1.333), respectively, (P<0.05). The hospitalized patients had a higher incidence of hemolysis (4.03% vs. 3.54%), lipemia (0.63% vs. 0.36%), and icterus (7.10% vs. 4.75%) than outpatients (P<0.001). Specimens with relatively longer transfer time and/or detection time had a higher HIL incidence (P<0.001). The Pediatrics had the highest incidence of hemolysis (16.2%) with an adjusted OR (AOR) of 4.93 (95%CI, 4.59-5.29, P<0.001). The Neonatology department had the highest icterus incidence (30.1%) with an AOR of 4.93 (95%CI: 4.59-5.29, P<0.001). The Neonatology department (2.32%) and Gastrointestinal Surgery (2.05%) had the highest lipemia incidence, with an AOR of 1.17 (95%CI: 0.91-1.51) and 4.76 (95%CI: 4.70-5.53), both P-value <0.001. There was an increasing tendency of hemolysis and icterus incidence for children under one year or adults aged more than 40., Conclusion: Evaluation of HIL incidence rate and HIL-related influence factors in fasting serum biochemistry specimens are impartment to interpret the results more accurately and provide better clinical services to patients., Competing Interests: The authors have declared that no competing interests exist.

Aims: Insulin sensitivity and insulin secretion can be estimated by multiple indices from fasting blood samples or blood samples obtained during oral glucose tolerance tests. The test-retest reliability of these indices in repeated measurements within the same individuals can strongly vary., Methods: We analyzed data of persons without diabetes who underwent two repeated OGTTs. For each measurement pair, we calculated multiple commonly used indices for the assessment of insulin secretion and insulin sensitivity. We then evaluated the coefficient of variation (standard deviation/mean) and discriminant ratio for each index., Results: 89 persons underwent two OGTTs with a median interval of 86 days (IQR 64-249). Among indices of insulin sensitivity derived from fasting blood samples, the revised quantitative insulin sensitivity check index had the smallest coefficient of variation (2.8 ± 2.1%) whereas the C-peptide based homeostasis model assessment 2 had the highest discriminant ratio (1.97 (1.65-2.39)). As for insulin sensitivity indices that are based on OGTT, the oral glucose insulin sensitivity index had the smallest coefficient of variation (6.5 ± 5.1%). The highest discriminant ratio was found for the non-esterified fatty acids-based insulin sensitivity index (NEFA-ISI, 2.70 (2.30-3.22)). For the assessment of insulin secretion from fasting variables, the lowest mean coefficient of variation was found for C-peptide based homeostasis model assessment 2 beta with 10.8 ± 8% and the highest discriminant ratio for the C-peptide / Glucose-Ratio (2.18 (1.84-2.63)). Among indices assessing insulin secretion from an OGTT, the lowest coefficient of variation was found for the ratio of the areas under the C-peptide and glucose curves from 0 to 120 minutes with 11.3 ± 9.7%., Conclusion: The data reveal large differences in the reproducibility and the discrimination capability of different indices that assess insulin sensitivity or insulin secretion. Our findings can aid the selection of an appropriate index in clinical studies., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: A fraction of children with obesity have increased serum cortisol levels. In this study, we describe the clinical characteristics of obese children and adolescents with elevated morning serum cortisol levels and the relationship between the cortisol levels and components of the metabolic syndrome., Methods: Retrospective medical record review study of children aged 4 to 18 years with overweight or obesity seen for obesity management in the Pediatric Obesity Clinic of the UZ Brussel between 2013 and 2015., Results: A total of 234 children (99 boys and 135 girls) with overweight (BMI z-score > 1.3) without underlying endocrine or genetic conditions were included. Mean (SD) age was 10.1 (2.8) years, BMI SD-score 2.5 (0.6), and body fat percentage 37% (7.9). Serum fasting cortisol levels were elevated (>180 μg/L) in 49 children, normal (62-180 μg/L) in 168, and decreased (<62 μg/L) in 12. Serum fasting cortisol was not significantly correlated with gender, age, or degree of adiposity. But correlated significantly with fasting glucose (Rs = 0.193; p < 0.005), triglycerides (Rs = 0. 143; p < 0.05), fibrinogen (Rs = 0.144; p < 0.05) and leptin levels (Rs = 0.145; p < 0.05). After adjustment for serum insulin and leptin, the correlation between serum cortisol and fasting glucose remained significant., Conclusion: Elevated morning serum cortisol levels were found in 20% of overweight or obese children and adolescents, irrespective of the degree of adiposity, and were associated with higher fasting glucose, irrespective of underlying insulin resistance. The long-term cardiometabolic consequences of hypercortisolemia in childhood obesity needs further study., Competing Interests: The authors have declared that no competing interests exist.

Coronary heart disease (CHD) is a prevalent complication of type 2 diabetes mellitus (T2DM). The atherogenic low-density lipoprotein (LDL) cholesterol is an established risk factor of cardiovascular disease, and evidence also suggests that postprandial plasma glucose (PPG) levels closely delineate CHD mortality in diabetes. The investigators hypothesized that postprandial plasma glucose excursion (PPGE), defined as the difference between 2-hour PPG and fasting plasma glucose (FPG), may be associated with plasma LDL cholesterol levels in patients with T2DM. This study enrolled diabetic participants for whom FPG and lipid profile were sampled after a 12-hour fast, followed by PPG sampling two hours after consuming a standard meal with 75 grams of carbohydrates. The study enrolled 379 participants who were divided into PPGE tertiles according to the difference between their 2-hour PPG and FPG. Participants in the highest PPGE tertile had considerably greater plasma LDL cholesterol levels than patients in the lowest tertile (126.7 mg/dL vs. 99.5 mg/dL, P <0.001). Linear regression analysis also demonstrated that the PPGE was positively correlated with plasma LDL cholesterol levels (β coefficient: 0.165, P < 0.001). Postprandial glucose excursion positively correlated with plasma LDL cholesterol levels in individuals with T2DM. Participants with raised PPGE harbored greater LDL cholesterol levels than those with lower postprandial glucose fluctuations. Therefore, postprandial glucose excursion is associated with an atherogenic lipid profile and may be a modifiable risk factor of diabetic CHD., Competing Interests: The authors have declared that no competing interests exist.

Background: Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD., Research Question: Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA?, Study Design and Methods: Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases., Results: 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40-9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16-8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94-11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19-2.38), p-value for interaction = 0.07., Interpretation: In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events., Competing Interests: The authors have declared no competing interests exist.

Importance: Patients with diabetes are known to be at increased risk for infections including severe coronavirus disease 2019 (COVID-19) but the relationship between COVID-19 severity and specific pre-infection glucose levels is not known., Objective: To assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes., Design: Population based historical cohort study., Setting: National state-mandated HMO., Patients: All adult patients with a positive SARS-COV2 test between March-October 2020., Exposure: Recent fasting blood glucose (FBG) and glycated hemoglobin (HBA1C), age, gender, body mass index (BMI) and diagnoses of diabetes, hypertension, ischemic heart disease., Outcome: Risk for severe COVID-19, defined as resulting in ≥10 hospitalization days, ICU admission or death., Results: 37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09-1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06-1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m2 increase, 95% CI 1.00-1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106-125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04-2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106-125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG (<100mg/dl) or HbA1C (<5.7%)., Conclusions and Relevance: Elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification., Competing Interests: The authors have declared that no competing interests exist.

We investigated the association between oral hygiene indicators of periodontitis, tooth loss, and tooth brushing on the longitudinal fasting glucose level in non-diabetic subjects. Using a nationwide health screening database in Korea, we included non-diabetic individuals who received a health screening program with oral health check in 2009-2010. We constructed a linear mixed model for the longitudinal data of fasting glucose from the baseline to 2015. During the 4.84-year of median follow-up, 91,963 individuals (mean age 56.2 at baseline) underwent 392,780 health examinations with fasting glucose level (mmol/L). The presence of periodontitis was 39.3%. In the multivariate linear mixed analysis, periodontitis was related with increased fasting glucose levels (β = 0.0084, standard error = 0.0035, p = 0.018). Similarly, tooth loss was associated with increased level of fasting glucose (β = 0.0246, standard error = 0.0038, p < 0.001). Compared with tooth brushing ≤2 times/day, tooth brushing ≥3 times/day was associated with decreased fasting glucose levels (β = -0.0207, standard error = 0.0033, p < 0.001). Our data showed that periodontitis and tooth loss were associated with increased fasting glucose levels in non-diabetic individuals. The study findings imply that frequent tooth brushing may reduce fasting glucose levels. Further research is needed to determine the effect of periodontal intervention on glycemic control., Competing Interests: The authors have declared that no competing interests exist.

Background: Insulin resistance (IR) has been considered as a therapeutic target in the management of type 2 diabetes mellitus (T2DM). Readily available, simple and low cost measures to identify individuals with IR is of utmost importance for clinicians to plan optimal management strategies. Research on the associations between surrogate markers of IR and routine clinical and lipid parameters have not been carried out in Sri Lanka, a developing country with rising burden of T2DM with inadequate resources. Therefore, we aimed to study the utility of readily available clinical parameters such as age, body mass index (BMI), waist circumference (WC) and triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) in the fasting lipid profile in predicting IR in a cohort of patients with newly diagnosed T2DM in Sri Lanka., Methods and Findings: We conducted a community based cross sectional study involving of 147 patients (age 30-60 years) with newly diagnosed T2DM in a suburban locality in Galle district, Sri Lanka. Data on age, BMI, WC, fasting plasma glucose (FPG) concentration, fasting insulin concentration and serum lipid profile were collected from each subject. The indirect IR indices namely homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI) and McAuley index (MCA) were estimated. Both clinical and biochemical parameters across the lowest and the highest fasting insulin quartiles were compared using independent sample t-test. Linear correlation analysis was performed to assess the correlation between selected clinical parameters and indirect IR indices. The area under the receiver operating characteristic (ROC) curve was obtained to calculate optimal cut-off values for the clinical markers to differentiate IR. BMI (p<0.001) and WC (p = 0.01) were significantly increased whereas age (p = 0.06) was decreased and TG/HDL-C (p = 0.28) was increased across the insulin quartiles. BMI and WC were significantly correlated (p<0.05) with HOMA, QUICKI and MCA. Out of the clinical parameters, age showed a borderline significant correlation with QUICKI and TG/HDL-C showed a significant correlation only with MCA. The area under ROC of BMI was 0.728 (95% CI 0.648-0.809; p<0.001) and for WC, it was 0.646 (95% CI 0.559-0.734; p = 0.003). The optimized cut-off value for BMI and WC were 24.91 kg/m2 and 81.5 cm respectively to differentiate the patients with IR or ID. Study limitations include small sample size due to recruitment of patients only from a limited geographical locality of the country and not totally excluding of the possibility of inclusion of some patients with slowly progressive type 1 DM or Latent onset diabetes of adulthood from the study population., Conclusions: The results revealed that there was a significant positive correlation between BMI, WC and HOMA while a significant negative correlation with QUICKI and MCA among the cohort of patients with newly diagnosed T2DM. The cut-off values of BMI and WC as 24.91 kg/m2 and 81.5 cm respectively could be used as simple clinical parameters to identify IR in newly diagnosed patients with T2DM. Our results could be beneficial in rational decision making in the management of newly diagnosed patients with T2DM in limited resource settings., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects., Methods: Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination., Results: The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals., Conclusion: The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation., Competing Interests: The authors have declared that no competing interests exist.

Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D., Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders., Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose., Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk., Competing Interests: The authors have read the journal’s policy and have the following competing interests: IP is employed by Eli Lilly Regional Operations GmbH, Vienna, Austria and BJ and HR are employees of Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt am Main, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Obesity is associated with lower 25-hydroxyvitamin D (25OHD) levels, but the association between 25OHD deficiency and specific body composition (BC) patterns remains unclear. The aim of this study was to analyze the correlation between 25OHD levels and BC in a population of healthy, nonobese individuals. Cross-sectional, observational study including a convenience sample of community-dwelling healthy individuals aged ≥18 years who responded to a study advertisement and were randomly selected. The participants filled out a questionnaire and had fasting blood drawn and anthropometric indices taken. Dual-energy x-ray absorptiometry was performed for BC analysis (fat and lean body mass). The subjects were divided according to 25OHD levels into three groups: I (≤20 ng/mL, vitamin D deficient), II (>20 and <30 ng/mL, vitamin D insufficient), and III (≥30 ng/mL, vitamin D sufficient). Of 299 individuals selected, 51 were excluded, yielding a final sample of 248 (128 women) who had serum 25OHD levels measured. Women presented higher 25OHD levels than men (27.8±12.0 ng/mL and 24.8±11.3 ng/mL, respectively; p = 0.03). Including both sexes, Group I had greater body mass index (BMI; 26.6±2.5 kg/m2) and waist circumference (WC; 91.8.8±9.1 cm) compared with the other groups. Group I also had 75.7% and 65.3% of abnormal BMI and WC values, respectively, (p<0.05 for both) and a higher percentage of trunk and android fat confirmed by multivariate analysis. No differences in BC were observed in individuals with insufficient versus sufficient 25OHD levels. Individuals with lower 25OHD levels had increased fat in the android region and trunk. This study confirms the association of lower 25OHD levels with greater BMI and WC and increased deposition of fat in body compartments, which, even in nonobese individuals, are commonly associated with increased metabolic risk., Competing Interests: The authors have declared that no competing interests exist.

Background: Women with hyperglycaemia first detected in pregnancy (HFDP), including those with gestational diabetes mellitus (GDM), should undergo a glucose evaluation 4-12 weeks after delivery. Globally, suboptimal postpartum return rates limit the opportunity to intervene in women with sustained hyperglycaemia and pragmatic solutions should be sought to bridge this gap., Objective: To assess the utility of postpartum in-hospital glucose evaluation to predict the outcome of the oral glucose tolerance test (OGTT) performed 4-12 weeks after delivery., Methods: The study was performed prospectively at Tygerberg Hospital, Cape Town, South Africa. Women with HFDP, classified as GDM based on the modified National Institute for Health and Care Excellence criteria, who delivered between November 2018 and June 2019 were included in the study. Fasting plasma glucose (FPG) was performed 24-72 hours after delivery (t1) in the postnatal ward, provided glucose lowering medication was discontinued at delivery. An OGTT 4-12 weeks postpartum (t2) was scheduled for the total cohort. We compared glucose values and glucose categories at t1 and t2 and evaluated antenatal characteristics of women who returned, compared to the group that was lost to follow-up., Results: In-hospital post-delivery glucose assessment (t1) was performed in 115 women. Glucose levels were significantly lower at t1 compared to antenatal diagnostic values (t0) and assessment at t2. Of the fourteen women with hyperglycaemia at t2, none had abnormal fasting glucose concentrations at t1. Women with HFDP who fulfilled criteria for overt diabetes at t0, all (24/115) had normal fasting glucose levels at t1 except for IFG in one (1/24). The antenatal characteristics of women with HFDP who returned at t2, were similar to the women who did not return., Conclusion: Based on this study, in-hospital fasting glucose 24-72 hours postpartum cannot replace the OGTT 4-12 weeks postpartum. Pragmatic solutions for low postpartum return rates in women with HFDP should be pursued., Competing Interests: The authors have declared that no competing interests exist.

Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals., Competing Interests: The authors have declared that no competing interests exist.

Background: Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes., Methods: Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm)., Results: At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state., Conclusions: DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people., Competing Interests: The authors declare they have no competing interests.

Aim: The addition of maternal age to fasting plasma glucose (FPG) at 24-28 gestational weeks improves the performance of GDM screening as maternal age increases. However, this method delays the diagnosis of GDM. Since FPG at the first prenatal visit (FPV) is a screening option for pre-existing diabetes, we evaluated the performance of age plus FPG at the FPV to reduce the need for the OGTT., Methods: Pregnant women were recruited consecutively in 2013-2018 (the training cohort) and 2019 (the validation cohort). We excluded women with twin pregnancies, unavailable FPG at the FPV or OGTT data, pre-pregnancy diabetes, or a history of GDM. All participants underwent FPG and haemoglobin A1c (HbA1c) at the FPV and received 75-g OGTT at 24-28 gestational weeks if FPG at the FPV was <92 mg/dL. GDM was diagnosed by the IADPSG criteria. Two algorithms were developed with the cutoffs determined when the percentage requiring OGTT (OGTT%) was the lowest and the sensitivity was ≥90%., Results: The incidence of GDM increased with age. The "FPG at the FPV" algorithm reduced OGTT% to 68.8% with the FPG cutoff at 79 mg/dl. The "age plus FPG at the FPV" algorithm, with the cutoff of 114, further reduced OGTT% to 58.3%, with the sensitivity of 90.7% (9.3% GDM missed) and the specificity of 100%. These findings were replicated in the validation cohort., Conclusions: Screening GDM by maternal age plus FPG at the FPV can reduce OGTT%, especially in populations with a significant proportion of pregnant women with advanced ages., Competing Interests: The authors have declared that no competing interests exist.

Aim: Fibroblast growth factor 21 (FGF21) has recently been implicated in thirst in rodent models. The mechanisms for this are currently uncertain, and it is unclear whether hydration status can alter FGF21 concentrations, potentially providing an additional mechanism by which hypohydration induces thirst. The aim of this study is therefore to understand whether hydration status can alter circulating FGF21 in humans., Methods: Using a heat tent and fluid restriction, we induced hypohydration (1.9% body mass loss) in 16 healthy participants (n = 8 men), and compared their glycaemic regulation to a rehydration protocol (heat tent and fluid replacement) in a randomised crossover design., Results: After the hypohydration procedure, urine specific gravity, urine and serum osmolality, and plasma copeptin (as a marker for arginine vasopressin) increased as expected, with no change after the rehydration protocol. In the fasted state, the median paired difference in plasma FGF21 concentrations from the rehydrated to hypohydrated trial arm was -37 (interquartile range -125, 10) pg∙mL-1(P = 0.278), with average concentrations being 458 ± 462 pg∙mL-1 after hypohydration and 467 ± 438 pg∙mL-1 after rehydration; mean difference -9 ± 173 pg∙mL-1., Conclusion: To our knowledge, these are the first causal data in humans investigating hydration and FGF21, demonstrating that an acute bout of hypohydration does not impact fasted plasma FGF21 concentrations. These data may suggest that whilst previous research has found FGF21 administration can induce thirst and drinking behaviours, a physiological state implicated in increased thirst (hypohydration) does not appear to impact plasma FGF21 concentrations in humans., Competing Interests: HAC has received conference fees, travel and accommodation (2016, 2017, 2018, and 2019) from Danone Nutricia, has run a Tate and Lyle sponsored study, and has received funding from Esther Olssons II & Anna Jönssons Minnesfond foundations. JAB has received funding from the BBSRC, GlaxoSmithKline, Lucozade Ribena Suntory, Kellogg’s, Nestlé, and PepsiCo. JAB is a scientific advisor to the International Life Sciences Institute (ILSI). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Aim: To investigate the relative contribution of phenotypic and lifestyle factors to HbA1c, independent of fasting plasma glucose (FPG) and 2h post-load glucose (2hPG), in the general population., Methods: The study populations included 2309 participants without known diabetes from the first wave of the Hoorn Study (1989) and 2619 from the second wave (2006). Multivariate linear regression models were used to analyze the relationship between potential determinants and HbA1c in addition to FPG and 2hPG. The multivariate model was derived in the first wave of the Hoorn Study, and replicated in the second wave., Results: In both cohorts, independent of FPG and 2hPG, higher age, female sex, larger waist circumference, and smoking were associated with a higher HbA1c level. Larger hip circumference, higher BMI, higher alcohol consumption and vitamin C intake were associated with a lower HbA1c level. FPG and 2hPG together explained 41.0% (first wave) and 53.0% (second wave) of the total variance in HbA1c. The combination of phenotypic and lifestyle determinants additionally explained 5.7% (first wave) and 3.9% (second wave)., Conclusions: This study suggests that, independent of glucose, phenotypic and lifestyle factors are associated with HbA1c, but the contribution is relatively small. These findings contribute to a better understanding of the low correlation between glucose levels and HbA1c in the general population., Competing Interests: The authors have read the journal’s policy and have the following competing interests: At the time this article was written, MA was a paid employee of Unilever, which manufactures and sells consumer food products. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors declare that they have no potential conflict of interests relevant to this article.

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p<1x10-7 (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests. Dr. Meigs currently has a research grant from GlaxoSmithKline and serves on a consultancy board for Interleukin Genetics. Dr. Florez has received consulting honoraria from Daiichi-Sankyo and AstraZeneca. Dr. Mike A. Nalls is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Nalls also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. DR. Jose C. Florez, Consulting honoraria from Janssen Pharmaceuticals and Goldfinch Bio, and speaking honorarium from Novo Nordisk The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Although the high disease burden that results from cardiovascular complications of hypertension, factors related to the progression to hypertension in the normotensive population are not actively reported. The purpose of this study was to estimate the rate of the progression to hypertension and to reveal the associated risk factors., Methods: The study included normotensive participants from the National Health Insurance Service-National Health Screening Cohort, and contained a 10% sample of all adults who received a national health screening test in either 2002 or 2003. At the end of the study in 2015, the patients were divided into two groups based on whether or not they progressed to hypertension. Cox proportional hazard modeling was performed to identify risk factors for progression. Subgroup analysis using logistic regression was employed to reveal factors influencing the different natural history of the progression., Results: Among the 75,335 included participants, the progression rate to hypertension was 66.39% (50,013), with an adjusted incidence rate of 8.62 per 100 person-year in the aged 40-64 group and 12.68 in the aged 65 or above group. Age, BMI, hemoglobin, and family history of hypertension and other diseases were related to the progression. Among the progression group, 78.21% (39,116) participants skipped a pre-hypertensive status; this group consisted of older females with lower pulse pressure and more alcohol consumption compared to people who had pre-hypertensive status before the progression., Conclusion: Substantial risk factors for the progression to hypertension should be carefully managed even in normotensive participants who receive health screening tests., Competing Interests: The authors have declared that no competing interests exist.

Our study revisits the role of cardiac mitochondrial adjustments during the progression of type 2 diabetes mellitus (T2DM), while considering age and sex as potential confounding factors. We used the Nile Grass rats (NRs) as the animal model. After weaning, animals were fed either a Standard Rodent Chow Diet (SRCD group) or a Mazuri Chinchilla Diet (MCD group) consisting of high-fiber and low-fat content. Both males and females in the SRCD group, exhibited increased body mass, body mass index, and plasma insulin compared to the MCD group animals. However, the females were able to preserve their fasting blood glucose throughout the age range on both diets, while the males showed significant hyperglycemia starting at 6 months in the SRCD group. In the males, a higher citrate synthase activity-a marker of mitochondrial content-was measured at 2 months in the SRCD compared to the MCD group, and this was followed by a decline with age in the SRCD group only. In contrast, females preserved their mitochondrial content throughout the age range. In the males exclusively, the complex IV capacity expressed independently of mitochondrial content varied with age in a diet-specific pattern; the capacity was elevated at 2 months in the SRCD group, and at 6 months in the MCD group. In addition, females, but not males, were able to adjust their capacity to oxidize long-chain fatty acid in accordance with the fat content of the diet. Our results show clear sexual dimorphism in the variation of mitochondrial content and oxidative phosphorylation capacity with diet and age. The SRCD not only leads to T2DM but also exacerbates age-related cardiac mitochondrial defects. These observations, specific to male NRs, might reflect deleterious dietary-induced changes on their metabolism making them more prone to the cardiovascular consequences of aging and T2DM., Competing Interests: The authors have declared that no competing interests exist.

Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport., Competing Interests: Yoshiaki Morishita, Yusuke Seino, and Yoji Hamada belonged to the Department of Metabolic Medicine, which was established by a donation from the Sanwa Kagaku Co. Ltd. Yoshihiro Ito belongs to the Department of Nephrology/CKD initiatives, which receives donations from the Sanwa Kagaku Co. Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: This study aimed to investigate whether different levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) in prediabetes are associated with hyperfiltration., Methods: A prospective cohort of 2,022 individuals aged 30-74 years took part in the PREDAPS Study. One cohort of 1,184 participants with prediabetes and another cohort of 838 participants with normal FPG and normal HbA1c were followed for 5 years. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile for healthy control participants, while hypofiltration was defined as an eGFR below the 5th percentile. The prevalence of hyperfiltration was compared for different levels of prediabetes: level 1 of prediabetes: FPG <100 mg/dL plus HbA1c 5.7-6.0% or FPG 100-109 mg/dL plus HbA1c < 5.7%; level 2 of prediabetes: FPG <100 mg/dL plus HbA1c 6.1-6.4% or FPG 100-109 mg/dL plus HbA1c 5.7-6.0% or FPG 110-125 mg/dL plus HbA1c <5.7% and level 3 of prediabetes: FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4%., Results: The participants with hyperfiltration were significantly younger, had a higher percentage of active smokers, and lower levels of hemoglobin and less use of ACEIs or ARBs. Only level 3 prediabetes based on FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4% had a significantly higher odds ratio (OR) of hyperfiltration (OR 1.69 (1.05-2.74); P < 0.001) compared with no prediabetes (FPG < 100 mg/dL and HbA1c < 5.7%) after adjustment for different factors. The odds ratios for different levels of HbA1c alone in prediabetes increased progressively, but not significantly., Conclusions: Level 3 of prediabetes based on FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4% had a significantly higher OR of hyperfiltration compared with participants without prediabetes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Ethiopia recorded the highest numbers of people with diabetes in Africa. It is not uncommon for diabetic patients to have poor glycemic control leading to a number of complications. The aim of this systematic review and meta-analysis is to evaluate the level of glycemic control among diabetic patients in Ethiopia by combining the studies from the existing literature., Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was employed to plan and conduct this review. A comprehensive electronic-based literature search was conducted in the databases of MEDLINE, HINARI, GOOGLE SCHOLAR, and SCIENCEDIRECT. Open meta-analyst software was used to perform meta-analyses. Proportions of good glycemic control among diabetic patients was calculated. Odds ratio was also calculated to check the presence of statistically significant difference in glycemic control among patients with type 1 and type 2 diabetes., Results: A total of 22 studies were included in the final analysis. Meta-analysis of 16 studies showed that only one-third of patients [34.4% (95% CI: 27.9%-40.9%), p<0.001] achieving good glycemic control based on fasting plasma glucose measurements. Similar to the studies that used fasting plasma glucose, the rate of good glycemic control was found to be 33.2% [(95% CI: 21.8%-44.6%), p<0.001] based on glycosylated hemoglobin measurements. There was no statistically significant difference in the rates of glycemic control between patients with type 1 and type 2 diabetes (p = 0.167)., Conclusion: High proportion of diabetic patients were unable to achieve good glycemic control. There was no difference in glycemic control among type 1 and type 2 diabetic patients., Competing Interests: The authors have declared that no competing interests exist.

Introduction: It is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research., Objectives: We quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using 1H NMR spectroscopy in plasma samples., Methods: In the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (<6 months) and long-term (>3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements., Results: Both fasting and postprandial metabolite concentrations showed high technical reproducibility using 1H NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0×10-14). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66., Conclusion: Technical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dennis Mook-Kanamori is a part-time clinical research consultant for Metabolon, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have nothing to disclose.

Background: Insulin resistance and related metabolic disturbances are major risk factors for the higher T2D risk and associated morbidity and mortality amongst South Asians. The contribution of physical activity to the increased prevalence of insulin resistance and related disturbances amongst South Asians is unknown., Methods: We recruited 902 South Asian and European men and women, aged 35-85 years from the ongoing LOLIPOP study. Clinical characterisation comprised standardised questionnaire and measurement of height, weight, waist and hip circumference and blood pressure. Fasting bloods were taken for assessment of glucose, insulin, lipids and HbA1c. Physical activity was quantified using a validated accelerometer, Actigraph GT3X+, worn for 7 days. Univariate and multivariate approaches were used to investigate the relationship between ethnicity, physical activity, insulin resistance and related metabolic disturbances., Results: Total physical activity was ~31% (P = 0.01) lower amongst South Asians compared to Europeans (Mean MET.minutes [SD]: 1505.2 [52] vs. 2050.9 [86.6], P<0.001). After adjusting for age and sex, total physical activity had a negative association with HOMA-IR (B [SE]: -0.18 [0.08], P = 0.04) and fasting glucose levels (B[SE]: -0.11 [0.04], P = 0.02). There was no association between physical activity and other glycemic and lipid parameters. Total physical activity per week contributed towards the differences in insulin resistance and associated metabolic disturbances between South Asians and Europeans., Conclusion: Lower levels of physical activity may contribute to the increased insulin resistance in South Asians compared to Europeans. Our results suggest that lifestyle modification through increased physical activity may help to improve glucose metabolism and reduce the burden of excess T2D and related complications amongst South Asians., Competing Interests: The authors have declared that no competing interests exist.

Objective: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status., Methods: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO)., Results: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0., Conclusion: Metabolic health is more closely associated with impaired lung function than obesity., Competing Interests: The authors have declared that no competing interests exist.

Only few studies document longer periods of fasting in large cohorts including non-obese participants. The aim of this study was to document prospectively the safety and any changes in basic health and well-being indicators during Buchinger periodic fasting within a specialised clinic. In a one-year observational study 1422 subjects participated in a fasting program consisting of fasting periods of between 4 and 21 days. Subjects were grouped in fasting period lengths of 5, 10, 15 and 20±2 days. The participants fasted according to the Buchinger guidelines with a daily caloric intake of 200-250 kcal accompanied by a moderate-intensity lifestyle program. Clinical parameters as well as adverse effects and well-being were documented daily. Blood examinations before and at the end of the fasting period complemented the pre-post analysis using mixed-effects linear models. Significant reductions in weight, abdominal circumference and blood pressure were observed in the whole group (each p<0.001). A beneficial modulating effect of fasting on blood lipids, glucoregulation and further general health-related blood parameters was shown. In all groups, fasting led to a decrease in blood glucose levels to low norm range and to an increase in ketone bodies levels (each p<0.001), documenting the metabolic switch. An increase in physical and emotional well-being (each p<0.001) and an absence of hunger feeling in 93.2% of the subjects supported the feasibility of prolonged fasting. Among the 404 subjects with pre-existing health-complaints, 341 (84.4%) reported an improvement. Adverse effects were reported in less than 1% of the participants. The results from 1422 subjects showed for the first time that Buchinger periodic fasting lasting from 4 to 21 days is safe and well tolerated. It led to enhancement of emotional and physical well-being and improvements in relevant cardiovascular and general risk factors, as well as subjective health complaints., Competing Interests: FWT is member of the Directory Board of the Buchinger Wilhelmi Clinic (BWC), where the study was performed. As managing director of Amplius GmbH, FWT executes the scientific leadership at BWC. Amplius GmbH is a company that conceives, coordinates and develops fasting research on behalf of BWC. FG is currently employed, and SD was formerly employed, at BWC. AM is a consultant at BWC and receives financial compensation for this role from Amplius GmbH. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Resveratrol, a non-flavonoid polyphenolic compound, is structurally and functionally similar to estrogen and has drawn great attention for its potentially beneficial effects on diabetes. However, it is not known whether it shares the same protective effect against diabetes as estrogen and the underlying mechanisms. The aim of the present study was to investigate the protective effects of phytoestrogen resveratrol and exogenous 17β-estradiol against streptozotocin (STZ)-induced type 1 diabetes. Female mice were ovariectomized (OVX) and chronically injected with different concentrations of resveratrol (0.1, 1 or 10 mg/kg) and 17β-estradiol (0.01, 0.1 or 1 mg/kg) subcutaneously for 4 weeks, and the levels of blood glucose, plasma insulin, plasma antioxidant capacity, the changes of pancreatic islet cells and the expressions of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and phosphorylation of extracellular signal-regulated kinase (p-ERK) were detected. Resveratrol and 17β-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ-induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue. The results suggest that resveratrol or 17β-estradiol shows obvious protection against STZ-induced diabetes in OVX mice, the mechanisms probably involve their ameliorating antioxidant activities and islet function, promoting muscle glucose uptake and inhibiting the expression of p-ERK., Competing Interests: The authors have declared that no competing interests exist.

Background: Single nucleotide polymorphisms (SNPs) in the 9p21 region have been associated with cardiovascular disease (CVD), but previous studies have focussed on older populations. The objective of this study was to determine the association between 9p21 genotypes and biomarkers of CVD risk in young adults from different ethnocultural groups., Methods: Subjects were 1,626 participants aged 20-29 years from the Toronto Nutrigenomics and Health Study. Fasting blood was collected to measure glucose, insulin, c-reactive protein and serum lipids, as well as to isolate DNA for genotyping subjects for five SNPs in 9p21. Analyses were conducted for the entire population and separately for women (n = 1,109), men (n = 517), Caucasians (n = 771), East Asians (n = 561) South Asians (n = 175) and Others (n = 119). ANOVA and ANCOVA were used to examine if 9p21 genotypes were associated with biomarkers of CVD risk., Results: In the entire group, the risk alleles of rs10757278 and rs2383206 were associated with higher mean insulin (p = 0.01). Risk alleles for rs4977574, rs10757278, rs2383206, rs1333049 and rs10757274 were associated with higher serum insulin in women (p = 0.008, p = 0.008, p = 0.0003, p = 0.002, and p = 0.001, respectively), but not in men (p = 0.41, p = 0.13, p = 0.31, p = 0.34, and 0.35, respectively). The association between 9p21 and insulin remained significant among women not taking hormonal contraceptives (HC), but was not significant among women taking HCs., Conclusion: Our findings suggest that 9p21 genotypes may play a role in the development of insulin resistance in early adulthood among women, but not men, and the effects appear to be attenuated by HC use., Competing Interests: AE-S holds shares in Nutrigenomix Inc. SM & DJ have no conflicts of interest to declare. All the authors had unrestricted access to all the data. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Introduction: Postprandial hyperglycemia plays a pivotal role in cardiovascular disease. However, few studies have investigated associations between the severity of coronary artery disease (CAD) and postprandial glucose levels in angina patients without known diabetes before coronary angiography., Methods: Subjects who were admitted for coronary angiography due to angina and were in stable condition after discharge were recruited. A standard 75-g oral glucose tolerance test (OGTT) was performed at outpatient visits approximately 2-4 weeks after hospital discharge, and fasting and post-challenge blood glucose were measured. Twenty-six volunteers in our hospital staff served as the healthy group. CAD severity was graded using the SYNTAX and Jeopardy scoring systems., Results: The subjects in the angina group had a higher body mass index, higher fasting glucose, and higher 2-h postprandial glucose than those in the healthy group. The SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not with fasting glucose. Linear regression analyses revealed that SYNTAX and Jeopardy scores were independently associated with glucose levels at 120 min after OGTT (SYNTAX 95%CI = 0.003-0.103; Jeopardy score 0.002-0.027) but not with fasting glucose., Conclusion: CAD severity is associated with blood glucose levels after oral glucose challenge in patients without known diabetes before coronary angiography, suggesting that CAD patients should be routinely screened for post-challenge blood glucose., Competing Interests: The authors have declared that no competing interests exist.

The negative effects of high normal glucose on cognitive function were previously reported in euglycemic individuals of middle age and the elderly population. This study aimed at examining the effect of baseline blood glucose levels on spatial ability, specifically verticality perception on the computerized rod and frame test (CRFT) in young healthy adults. 63 healthy male medical students (age range from 18-23 years), of whom 30 were non-fasting outside the month of Ramadan and 33 fasting during Ramadan of the year 2016, were recruited in order to create varying degrees of glycemia during which verticality perception was carried out. Baseline blood glucose reading was obtained prior to commencing the CRFT test. Blood glucose levels at the time of testing decreased as the duration between the last meal and testing increased. A blood glucose range of 62-117 mg/dl was achieved among participants for this study. Linear regression analysis showed that blood glucose level at testing correlated positively with all alignment spatial error parameters, indicating a probable reduction of spatial perception ability with higher blood glucose levels. These results are consistent with other cognitive studies in older healthy humans and emphasize the critical impact of early glucose dys-homeostasis on cognitive function. They also indicate that elevated blood glucose may affect cognitive functioning outside of the usual complications of diabetes., Competing Interests: The authors have declared that no competing interests exist.

Background: This study aims to explore retinal vessel calibre in individuals at risk of coronary artery disease (CAD), diagnosed with impaired fasting glucose (IFG) or diabetes mellitus (DM), and whether indices of CAD extent and severity modifies these associations with DM., Methods: A cross-sectional study was undertaken of 1680 patients presenting to Westmead Hospital (Sydney, Australia) for evaluation of potential CAD. Baseline digital retinal photographs, cardiovascular risk factor measurements, fasting blood tests and self-reported diabetes by patient questionnaire was recorded. Extent and severity of CAD was assessed using Extent and Gensini scores from angiography findings, respectively. Multivariate analysis including age and hypertension was undertaken to assess the association between retinal vessel calibre and IFG or DM., Results: A total of 748 patients were included; 96 (12.8%) and 189 (25.3%), respectively, had IFG or DM (together termed 'hyperglycaemia'). No consistent association between hyperglycaemia and retinal arteriolar calibre was apparent. Wider retinal venular calibre (second and third tertile) carried a significantly higher odds of DM in men only (multivariable-adjusted OR 2.447, p = 0.005; and OR 2.76, p = 0.002; respectively). No equivalent association was apparent in women. This association was marginally significant (p = 0.08) in patients with CAD Extent scores below the median (i.e. less diffuse CAD). Retinal vessel calibre was not associated with impaired fasting glucose., Conclusions: This study reports a significant association between retinal venular widening and diabetes mellitus in men. This association was marginally stronger among participants with less diffuse CAD.

Introduction: Guidelines recommend early detection of type 2 diabetes mellitus (DM2). The objective of the present study was to evaluate the capacity to identify DM2 in subjects that were screened for DM2 simultaneously with all three of the tests recommended-fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and a 2-hour post 75-g oral glucose tolerance test (OGTT)., Methods and Results: The present analysis of an anonymous database of 1113 adults from a reference clinical laboratory in Bucaramanga, Colombia, was an observational, descriptive, cross-sectional secondary source study. 259 individuals met at least one of the criteria for DM2: FPG ≥ 126mg/dL (7.0mmol/L), HbA1c ≥ 6.5% (48mmol/mol) and OGTT ≥ 200mg/dL (11.1mmol/L). 30 subjects (2.7%) were diabetic according to FPG, 56 subjects (5.0%) by HbA1c and 250 subjects (22.5%) by OGTT. In total 259 subjects (23.3% [IC 95%: 20.7%- 25.8%] were diabetic either by FPG, OGTT or HbA1c., Discussion: The largest number of patients were identified as diabetic with the OGTT. The combination of two or three tests did not increase the detection of new cases of DM2. Our findings suggest that routinely requesting FPG, OGTT and HbA1c at the same time may be inappropriate in at risk individuals, as this approach does not significantly improve the diagnostic capacity compared to using FPG+OGTT and substantially increases the financial burden on the health system, insurers or individual.

Epidemiological studies have revealed that noise exposure was associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of that association remains to be elucidated. The present study is designed to examine the effects of chronic noise exposure on the development of T2DM in combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J male mice, including worsened glucose intolerance, insulin resistance, fasting hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a paradoxical impact on fat accumulation and circulating levels of free fatty acid, indicating a potential stimulating effect of noise on lipolysis. These results provide first in vivo supporting evidence for the causative role of noise exposure in diabetogenesis and pinpoint a noise-associated increase in blood free fatty acid levels as a possible mediator accelerating the effect of noise on the development of insulin resistance and T2DM.

Background: The prevalence of metabolic syndrome has markedly increased worldwide. However, studies in the United States show that it has remained stable or slightly declined in recent years. Whether this applies to other countries is presently unclear., Objectives: We examined the trends in the prevalence of metabolic syndrome and its components in Korea., Methods: The prevalence of metabolic syndrome and its components was estimated in adults aged >30 years from the Korean National Health Insurance Service data from 2009 to 2013. The revised National Cholesterol Education Program criteria were used to define metabolic syndrome., Results: Approximately 10 million individuals were analyzed annually. The age-adjusted prevalence of metabolic syndrome increased from 28.84% to 30.52%, and the increasing trend was more prominent in men. Prevalence of hypertriglyceridemia, low HDL-cholesterol, and impaired fasting plasma glucose significantly increased. However, the prevalence of hypertension decreased in both genders. The prevalence of abdominal obesity decreased in women over 50 years-of-age but significantly increased in young women and men (<50 years)., Conclusions: The prevalence of metabolic syndrome is still increasing in Korea. Trends in each component of metabolic syndrome are disparate according to the gender, or age groups. Notably, abdominal obesity among young adults increased significantly; thus, interventional strategies should be implemented particularly for this age group.

Aim: The present study evaluated the relative influence of body mass index (BMI) on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting plasma glucose level in an older ethnic Chinese population., Methods: In total, 265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L were enrolled. Participants had BMIs of 20.0-34.2 kg/m2. IR, FPIS, SPIS, and GE were estimated using our previously developed equations. Pearson correlation analysis was conducted to assess the correlations between the four diabetogenesis factors and BMI. A general linear model was used to determine the differences in the percentage of change among the four factor slopes against BMI., Results: Significant correlations were observed between BMI and FPIS, SPIS, IR, and GE in both women and men, which were higher than those reported previously. In men, BMI had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in women, the order was slightly different: IR, followed by FPIS, SPIS, and GE. Significant differences were observed among all these slopes, except for the slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p = 0.258)., Conclusions: The contribution of obesity to all diabetes factors, except GE, was higher than that reported previously. BMI had the most profound effect on insulin secretion in men and on IR in women in this 60-year-old cohort, suggesting that lifestyle modifications for obesity reduction in women remain the most important method for improving glucose metabolism and preventing future type 2 diabetes mellitus.

The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals., Design: Ten subjects [5 PD (age = 35±9.3 yr, BMI = 32.1±4.0, FBG = 101.8±1.3 mg/dl) and 5 CON (age = 31±9.4 yr, BMI = 29.4±5.2, FBG = 82.8±9.7 mg/dl)] had blood drawn for RNA isolation prior to exercise (Pre), immediately following acute moderate intensity exercise on a treadmill (Post-1), 6-hours post (Post-6), and 24-hours post (Post-24). Isolation of mRNA from PBMCs was performed using ficoll separation, while the profiling of mRNA expression was performed using Illumina beadchip arrays with standard protocols. Scan results were statistically analyzed for a specific list of genes related to GH and IGF-1. GH and IGF-1 protein levels were also assessed in each sample. To address issues of normality, all GH and IGF-1 data were log-transformed prior to analysis. Statistical significance was set at p<0.05., Results: Group differences for GH2 variant 2 (p = 0.070) and GH2 variant 3 (p = 0.059) were coupled with significant alterations in IGF-1 mRNA over time (p = 0.024). A significant interaction between group and time was observed for GHRH mRNA (p = 0.008). No group differences were observed in GH AUC (p = 0.649), ΔGH (p = 0.331), GHrec (p = 0.294), or IGF-1 AUC (p = 0.865), representing a similar exercise-induced GH and IGF-1 response for both groups., Conclusions: Analysis of GH and IGF-1 related-gene expression indicates that mild elevations in fasting blood glucose and exercise-induced alterations in gene expression are impacted by the prediabetic state.

Background: Insulin resistance, glucose intolerance and overt diabetes are known metabolic complications associated with chronic use of HIV-Protease Inhibitors. Naringin is a grapefruit-derived flavonoid with anti-diabetic, anti-dyslipidemia, anti-inflammatory and anti-oxidant activities., Objectives: The study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo., Methods: Male Wistar rats were divided into six groups (n = 6) and were daily orally treated with distilled water {3.0 ml/kg body weight (BW)}, atazanavir (133 mg/kg BW), saquinavir (333 mg/kg BW) with or without naringin (50 mg/kg BW), respectively for 56 days. Body weights and water consumption were recorded daily. Glucose tolerance tests were carried out on day 55 of the treatment and thereafter, the rats were sacrificed by halothane overdose., Results: Atazanavir (ATV)- or saquinavir (SQV)-treated rats exhibited significant weight loss, polydipsia, elevated Fasting blood glucose (FBG), reduced Fasting Plasma Insulin (FPI) and expression of phosphorylated, Insulin Receptor Substrate-1 (IRS-1) and Akt proteins, hepatic and pancreatic glucokinase levels, and also increasing pancreatic caspase-3 and -9 as well as UCP2 protein expressions compared to controls, respectively. These effects were completely reversed by naringin treatment., Conclusion: Naringin prevents PI-induced glucose intolerance and impairment of insulin signaling and as nutritional supplement it could therefore alleviate metabolic complications associated with antiretroviral therapy.

Background: While undernutrition and related infectious diseases are still pervasive in many developing countries, the prevalence of non-communicable diseases (NCD), typically associated with high body mass index (BMI), is rapidly rising. The fast spread of supermarkets and related shifts in diets were identified as possible factors contributing to overweight and obesity in developing countries. Potential effects of supermarkets on people's health have not been analyzed up till now., Objective: This study investigates the effects of purchasing food in supermarkets on people's BMI, as well as on health indicators such as fasting blood glucose (FBG), blood pressure (BP), and the metabolic syndrome., Design: This study uses cross-section observational data from urban Kenya. Demographic, anthropometric, and bio-medical data were collected from 550 randomly selected adults. Purchasing food in supermarkets is defined as a binary variable that takes a value of one if any food was purchased in supermarkets during the last 30 days. In a robustness check, the share of food purchased in supermarkets is defined as a continuous variable. Instrumental variable regressions are applied to control for confounding factors and establish causality., Results: Purchasing food in supermarkets contributes to higher BMI (+ 1.8 kg/m2) (P<0.01) and an increased probability (+ 20 percentage points) of being overweight or obese (P<0.01). Purchasing food in supermarkets also contributes to higher levels of FBG (+ 0.3 mmol/L) (P<0.01) and a higher likelihood (+ 16 percentage points) of suffering from pre-diabetes (P<0.01) and the metabolic syndrome (+ 7 percentage points) (P<0.01). Effects on BP could not be observed., Conclusions: Supermarkets and their food sales strategies seem to have direct effects on people's health. In addition to increasing overweight and obesity, supermarkets contribute to nutrition-related NCDs. Effects of supermarkets on nutrition and health can mainly be ascribed to changes in the composition of people's food choices.

Background: Type 2 diabetes and prediabetes are established risk factors for atherosclerosis. The aim of this study was to evaluate the atherosclerotic plaque burden in the carotid arteries of patients with acute coronary syndrome according to their glycemic status., Methods: Patients with acute coronary syndrome and no previous history of type 2 diabetes were consecutively included in the study. Glucose metabolism was evaluated with fasting glucose in plasma, HbA1c and a standard two-hour oral glucose tolerance test. Atherosclerotic plaque in the carotid arteries was evaluated with a standardized ultrasound examination where total plaque area was measured and patients classified as having no plaque or a significant plaque formation., Results: A total of 245 acute coronary syndrome patients (male 78%, 64 years (SD: 10.9)) were included. The proportion diagnosed with normal glucose metabolism, prediabetes and type 2 diabetes was 28.6%, 64.1% and 7.3%, respectively. A significant atherosclerotic plaque was found in 48.5%, 66.9% and 72.2% of patients with normal glucose metabolism, prediabetes and type 2 diabetes, respectively. An incremental increase in total plaque area was found from normal glucose metabolism to prediabetes (25.5%) and from normal glucose metabolism to type 2 diabetes (35.9%) (p = 0.04). When adjusted for conventional cardiovascular risk factors the OR of having significant atherosclerotic plaque in the carotid arteries was 2.17 (95% CI 1.15-4.15) for patients with newly diagnosed dysglycemia compared to patients with normal glucose metabolism. When additionally adjusted for the 2-hour plasma glucose after glucose loading (2hPG) the OR attenuated to 1.77 (95% CI 0.83-3.84)., Conclusion: Newly detected dysglycemia is an independent predictor of significant atherosclerotic plaque in the carotid arteries with oral glucose tolerance test as a major determinant of carotid plaque burden in this group of individuals with acute coronary syndrome.

Objective: HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population., Materials and Methods: The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%., Results: The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7-10.7%; n = 342) and 34.6% (33.0-36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5-7.2%; n = 223) and 12.1% (11.1-13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group., Conclusion: These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

Objective: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF)., Research Design and Methods: Fourteen common (minor allele frequencies ≥0.05) DPP4 tagging single nucleotide polymorphisms (SNPs) were genotyped in 1,976 non-diabetic TÜF participants characterized by oral glucose tolerance tests and bioimpedance measurements. In a subgroup of 168 subjects, plasma incretin levels were determined., Results: We identified a variant, i.e., SNP rs6741949, in intron 2 of the DPP4 gene that, after correction for multiple comparisons and appropriate adjustment, revealed a significant genotype-body fat interaction effect on glucose-stimulated plasma GLP-1 levels (p = 0.0021). Notably, no genotype-BMI interaction effects were detected (p = 0.8). After stratification for body fat content, the SNP negatively affected glucose-stimulated GLP-1 levels (p = 0.0229), insulin secretion (p = 0.0061), and glucose tolerance (p = 0.0208) in subjects with high body fat content only., Conclusions: A common variant, i.e., SNP rs6741949, in the DPP4 gene interacts with body adiposity and negatively affects glucose-stimulated GLP-1 levels, insulin secretion, and glucose tolerance. Whether this SNP underlies the reported inter-individual variance in responsiveness to DPP-4 inhibitors, at least in subjects with high body fat content, remains to be shown.

Metabolic syndrome (MetS) has an important epidemiological relevance due to its increasing prevalence and association with type 2 diabetes and cardiovascular disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust clinical and epidemiological marker of MetS. Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions; its levels decrease as number of components of MetS increases. High-molecular weight adiponectin (HMWA) is the multimer responsible for the relationship of adiponectin with insulin sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS and considered a better marker of its presence, than either HOMA-IR or adiponectin alone, in selected homogeneous populations. We compared the strength of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key components. Our data have shown that the median (25th, 75th percentile) of HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r) was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14, respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. These results expand on previous studies in that we used the active circulating form of adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome.

Protein and other compounds can exert anabolic effects on skeletal muscle, particularly in conjunction with exercise. The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based, multi-ingredient nutritional supplement to increase strength and lean mass independent of, and in combination with, exercise in healthy older men. Forty-nine healthy older men (age: 73 ± 1 years [mean ± SEM]; BMI: 28.5 ± 1.5 kg/m2) were randomly allocated to 20 weeks of twice daily consumption of either a nutritional supplement (SUPP; n = 25; 30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg calcium, and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid); or a control (n = 24; CON; 22 g of maltodextrin). The study had two phases. Phase 1 was 6 weeks of SUPP or CON alone. Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise: SUPP + EX or CON + EX. Isotonic strength (one repetition maximum [1RM]) and lean body mass (LBM) were the primary outcomes. In Phase 1 only the SUPP group gained strength (Σ1RM, SUPP: +14 ± 4 kg, CON: +3 ± 2 kg, P < 0.001) and lean mass (LBM, +1.2 ± 0.3 kg, CON: -0.1 ± 0.2 kg, P < 0.001). Although both groups gained strength during Phase 2, upon completion of the study upper body strength was greater in the SUPP group compared to the CON group (Σ upper body 1RM: 119 ± 4 vs. 109 ± 5 kg, P = 0.039). We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men. Increases in strength were enhanced further with exercise training., Trial Registration: ClinicalTrials.gov NCT02281331.