Nondiabetic Men Research Articles

Moderate alcohol consumption is associated with impaired insulin secretion and fasting glucose in non-obese non-diabetic men.

Aims/IntroductionA low insulin secretion capacity has been implicated in the high prevalence of non‐obese diabetes in East Asians. As alcohol consumption alters insulin and glucose metabolism, we tested the hypothesis that alcohol consumption contributes to impaired insulin secretion and glucose intolerance in lean/normal‐weight non‐diabetic Japanese men.Materials and MethodsThis cross‐sectional study was undertaken among the residents of Shika town, Japan, between 2011 and 2017. A total of 402 non‐diabetic men, including participants with normal fasting plasma glucose (FPG) and impaired FPG (FPG 5.6–6.9 mmol/L), and aged ≥40 years, were examined. FPG, the homeostasis model assessment of insulin secretion capacity (HOMA‐B) and alcohol consumption were evaluated and compared between the body mass index (BMI) <25 and BMI ≥25 groups.ResultsHOMA‐B levels were lower in the BMI <25 group than in the BMI ≥25 group. Alcohol consumption correlated with a low HOMA‐B level regardless of BMI, and, thus, the HOMA‐B levels of alcohol drinkers were significantly lower in the BMI <25 group. A multivariable logistic regression analysis showed that alcohol consumption, even light‐to‐moderate consumption (1–25 g/day), was associated with significantly low levels of HOMA‐B and impaired FPG in the BMI <25 group. Among participants with impaired FPG, a low level of HOMA‐B was observed in alcohol drinkers, but not in non‐drinkers. In contrast, light‐to‐moderate alcohol consumption was not related to HOMA‐B or FPG in the BMI ≥25‐group.ConclusionAlcohol consumption, even a small amount, might contribute to reductions in HOMA‐B levels and impaired FPG in lean/normal‐weight Japanese men.

Complex interplay among fat, lean tissue, bone mineral density and bone turnover markers in older men.

It has been suggested that visceral fat (VF) might be a negative determinant of bone health. The purpose of this cross-sectional study was to assess an interplay among fat, visceral fat (VF), muscle mass, bone mineral density (BMD), and markers of bone turnover in men aged 60-75 years. BMD, lean mass, total fat, VF and appendicular skeletal muscle mass (ASM) were assessed using dual-energy X-ray absorptiometry. Using ELISA assays, we measured serum levels of markers of bone turnover (osteocalcin, parathyroid hormone, human procollagen I N-terminal peptide, and degradation products of C-terminal telopeptide of type I collagen). Mean values of bone markers were within normal range. VF was found not to be associated with BMD and bone turnover markers. ASM was inversely correlated with age, and positively with BMD and lean mass. In linear regression, ASM, VF, total fat, lean mass and body mass index were significant single predictors of BMD. However, after adjustment for age, all these associations were no longer significant. In conclusion, in contrast to some studies on postmenopausal women, in older non-diabetic men with normal lean mass and body fat VF was not associated with BMD and markers of bone formation and resorption.

Association of Triglyceride-Glucose Index with Bone Mineral Density in Non-diabetic Koreans: KNHANES 2008–2011

The association of insulin resistance (IR), as indicated by the homeostasis model assessment of insulin resistance, with bone metabolism is yet to be clarified. We aimed to investigate the relationship of IR with bone mass by using the triglyceride-glucose (TyG) index as an alternative marker of IR. Data of 4810 non-diabetes individuals (2552 men aged ≥ 50years and 2258 postmenopausal women) from the Korean National Health and Nutritional Examination Survey IV and V were analyzed. Bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and whole body were measured using dual-energy X-ray absorptiometry. After adjusting for confounding factors, there were inverse relationships of TyG index with femoral neck, total hip, and whole body BMD in men (β = - 0.085, P < 0.001 at femoral neck; β = - 0.046, P = 0.037 at total hip; β = - 0.098, P < 0.001 at whole body). However, in women, femoral neck and whole body BMD were negatively associated with the TyG index (β = - 0.071, P = 0.008 at femoral neck and β = - 0.065, P = 0.005 at whole body). The highest TyG index tertile exhibited reduced femoral neck BMD in both sexes (P = 0.003 in men and P = 0.013 in women) and reduced whole body BMD in men (P < 0.001) after adjusting for confounders. When the study subjects were divided into BMI (body mass index) < 23kg/m2 and ≥ 23kg/m2 groups, the TyG index was significantly associated with femoral neck BMD only in the women with BMI < 23kg/m2 (P = 0.009). We observed a significant association between the highest TyG index tertile and low bone mass at the femoral neck in women with BMI < 23kg/m2 (P = 0.003) that was not observed in women with BMI ≥ 23kg/m2 and men. In conclusion, IR evaluated using the TyG index was inversely associated with femoral neck BMD in non-diabetic men aged ≥ 50years and postmenopausal women. The negative influence of IR on femoral neck BMD was robust in the women with BMI < 23kg/m2. This indicates a differential effect of IR on BMD according to skeletal site, sex, and BMI.

A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched Chain Amino Acids, is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort.

Objective: Evaluate the ability of a newly developed diabetes risk score, the Diabetes Risk Index (DRI), to predict incident type 2 diabetes mellitus (T2D) in a large adult population. Methods: The DRI was developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from 6 lipoprotein subspecies and size parameters, and the branched chain amino acids, valine and leucine, all of which have been shown previously to be associated with future T2D. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2D. Results: During a median follow-up of 8.5 years, 306 new T2D cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2D with the hazard ratio (HR) for the highest versus lowest quartile being 12.07 (95% confidence interval: 6.97–20.89, p < 0.001). After additional adjustment for body mass index (BMI), family history of T2D, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 3.20 (1.73–5.95), p = 0.001). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 (1.14–1.65), p < 0.001). The Kaplan–Meier plot demonstrated that patients in the highest quartile of DRI scores presented at higher risk (p-value for log-rank test <0.001). Conclusions: Higher DRI scores are associated with an increased risk of T2D. The association is independent of clinical risk factors for T2D including HOMA-IR, BMI and conventional lipids.

Relationship between sexual function and type 2 diabetes in infertile men referred to Royan institute

Introduction: Endocrine disorders are one of the causes of infertility and sexual dysfunction is one of the neurological complications of diabetes. Objectives: The present study investigated the relationship between sexual function and type 2 diabetes in infertile men referring to the Royan Institute in 2019. Patients and Methods: This cross-sectional study was conducted in 2019 on 150 non-diabetic infertile men and 126 diabetic infertile men who referred to the Royan institute and were qualified in terms of research inclusion criteria. The convenience sampling method was used. The tools used to collect data include a demographic checklist, an 11-item version of Sexual Quality of Life-Male (SQOL-M), and a 15-question International Index of Erectile Function (IIEF) Questionnaire. Results: A total of 276 people were evaluated in this study. The mean age of participants was 40.98 (7.44) years in the diabetic group and 35.2 (6.08) years in the non-diabetic group. Sexual function, failure to reach ultimate pleasure, sexual desire, satisfactory sexual intercourse, overall sexual satisfaction, erectile function, as well as the standard index of sexual quality of life (SQOL-M score) showed no statistically significant difference between diabetic and non-diabetic infertile men (P&gt; 0.05). In people with normal body mass index (BMI) and employees, the relationship between diabetes and the overall score of sexual function was statistically significant (P&lt; 0.05). In addition, there is a significant relationship between diabetes and the SQOL-M in people under 37 years of age and people with primary infertility (P&lt; 0.05). Conclusion: Age and BMI are the two main factors influencing sexual function. In the present study, statistical relationship of these two factors in two groups of diabetics and non-diabetic infertile men not in general but in subgroups was proved. Our investigation indicated no statistically significant relationship between the two groups of diabetic and non-diabetic infertile men in any of the factors of sexual function and the standard index of male quality of sexual life.

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus.

BackgroundErectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro.MethodsType 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins.ResultsAdministration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor.ConclusionLiraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.

Advanced lipoprotein profile disturbances in type 1 diabetes mellitus: a focus on LDL particles

BackgroundLipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profile in T1DM individuals, and analysed differences with non-diabetic counterparts.MethodsThis cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed.ResultsThe median (interquartile range) age of the study participants was 45 (38–53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16–31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p < 0.001). The T1DM group had a better conventional (all parameters, p < 0.001) and NMR-lipid profile than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p < 0.001 for all). While non-diabetic women had a more favourable lipid profile than non-diabetic men, women with T1DM had a similar concentration of LDL-particles compared to men with T1DM (1231 [1125–1383] vs. 1257 [1128–1383] nmol/L, p = 0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2–733.9] vs. 671.2 [593.5–761.4] nmol/L, respectively; p = 0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDL-cholesterol than non-diabetic subjects (prevalence of LDL-cholesterol < 100 mg/dL & LDL-particles > 1000 nmol/L: 38 vs. 21.2%; p < 0.001). All these differences were largely unchanged in participants without lipid-lowering drugs (T1DM, n = 275; controls, n = 317).ConclusionsOverall, T1DM participants showed a more favourable conventional and NMR-lipid profile than controls. However, the NMR-assessment identified several lipoprotein derangements in LDL-particles among the T1DM population (higher discrepancies in NMR-LDL-particles vs. conventional LDL-cholesterol; a worse profile in T1DM women) that were overlooked in the conventional analysis. Further studies are needed to elucidate their role in the development of CVD in this population.

Trigger Finger Treatment: Identifying Predictors of Nonadherence and Cost.

Evidence-based practices in medicine are linked with a higher quality of care and lower health care cost. For trigger finger, identifying patient factors associated with nonadherence to evidence-based practices will aid physicians in treatment decisions. The objectives were to (1) determine patient factors associated with treatment nonadherence, (2) examine the success rates of steroid injections, and (3) evaluate the economic consequences of nonadherence to treatment recommendations. The authors used data from the Clinformatics DataMart database from 2010 to 2017 to conduct a population-based analysis of patients with single-digit trigger finger. The authors calculated rates of steroid injection success and examined associations between injection success and patient factors using chi-square tests. In addition, the authors analyzed differences in the cost to the insurer, the cost to the patient, and total cost. A total of 29,722 patients were included in this analysis. Injection success rates were similar for diabetic (72 percent) and nondiabetic patients (73 percent), women (73 percent), and men (73 percent). Nonetheless, diabetics (OR, 1.4; 95 percent CI, 1.4 to 1.5; p < 0.001) and women (OR, 1.2; 95 percent CI, 1.1 to 1.2; p < 0.001) were significantly more likely to receive nonadherent treatment. In total, $23 million (U.S. dollars) were spent on nonadherent trigger finger care. Diabetics and women have increased odds of having surgery without a prior steroid injection, despite similar success rates of steroid injections compared to nondiabetics and men. Because performing surgical release before any steroid injections may represent a higher cost treatment option, providers should provide steroid injections before surgery for all patients regardless of diabetes status or sex to minimize overtreatment. Risk, III.

The Mechanism of Coronary Artery Calcification in Centrally Obese Non-Diabetic Men: Study on The Interaction of Leptin, Free Leptin Index, Adiponectin, hs-C Reactive Protein, Bone Morphogenetic Protein-2 and Matrix Gla Protein

Background: The calcium in the artery was thought to be the result of the imbalance or dysregulation of the promoter and inhibitor cytokines influenced by various subclinical and clinical conditions. This study aimed to investigate the interaction between central obesity, as an early subclinical condition, also known as a chronic low grade inflammation condition and coronary artery calcium (CAC) in non-diabetic population including the underlying pathomechanisms of a CAC in the early stage of atherosclerosis.Materials and Methods: This was a cross-sectional pathway analysis study enrolling 60 central obesity non-diabetic men that underwent coronary calcium score scan, anthropometrics and biomarker assays.Results: There was a positive correlation between increasing free leptin index/adiponectin (FLI/A) ratio and CAC (r=0.297; p&lt;0.05). There was a positive correlation between increasing FLI/A ratio and plasma high sensitive C-reactive protein (hs-CRP) (r=0.318; p&lt;0.05). Plasma hs-CRP and bone morphogenetic protein-2 (BMP-2)-matrix gla protein (MGP) dysregulation were positively correlated (r=0.221; p&lt;0.05) after adjusted to risk factors including insulin resistance, hypertension, age, and dyslipidemia.Conclusion: The study found that one of the pathways involved in CAC in the centrally obese non-diabetic male is might be due to an increase of free leptin and decrease of adiponectin. The free leptin and adiponection ratio also increased hs-CRP, which partially correlated to the dysregulation of BMP-2 and MGP.Keywords: coronary artery calcification, central obesity, adipokines, bone regulator protein, pathomechanism

Insulin-related dietary indices predict 24-h urinary C-peptide in adult men.

The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men's Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were calculated using validated FFQ. We conducted multivariable-adjusted linear regression to estimate relative and absolute concentrations of 24-h urinary C-peptide. In multivariable-adjusted models, we found a significant positive association between all three insulin-related dietary indices and 24-h urinary C-peptide (P < 0·05). Relative concentrations of 24-h urinary C-peptide per 1-sd increase in insulin-related dietary indices were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the association was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unchanged for dietary insulin index and dietary insulin load. In conclusion, EDIH, dietary insulin index and dietary insulin load were predictive of integrated insulin secretion assessed by 24-h urinary C-peptide. Findings after adjustment for BMI appear to confirm the relation of EDIH to insulin resistance and dietary insulin index/load to insulin secretion; the respective constructs of the two dietary indices.

1437-P: A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched-Chain Amino Acids, Is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort

Objective: Evaluate the ability of the Diabetes Risk Index (DRI) to predict incident type 2 diabetes mellitus (T2DM) in a large cohort. Methods: The DRI was developed by combining the 6 lipoprotein subfractions in the Lipoprotein Insulin Resistance Index (LP-IR) and the branched chain amino acids valine and leucine, all of which have been shown previously to be associated with future T2DM. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2DM. Results: During a median follow-up of 8.5 years, 306 new T2DM cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2DM with the hazard ratio (HR) for the highest versus lowest tertile being 7.49 (95% confidence interval: 5.01-11.19), P &amp;lt;0.001. After additional adjustment for BMI, family history of T2DM, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 1.67 [1.01-2.76], P = 0.04). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 [1.14-1.65], P = 0.001). The Kaplan-Meier plot demonstrated that patients in the highest tertile of DRI scores presented at higher risk (p-value for log-rank test &amp;lt;0.001). Conclusions: Higher DRI scores are associated with an increased risk of T2DM. The association is independent of clinical risk factors for T2DM including HOMA-IR, BMI and conventional lipids. Disclosure J. Flores-Guerrero: None. M.A. Connelly: Employee; Self; LabCorp. I.Y. Shalaurova: None. E.G. Gruppen: None. J.D. Otvos: Employee; Self; LabCorp. R.P.F. Dullaart: None. S.J.I. Bakker: None.

The association of diabetes with all-cause mortality in patients with end-stage renal disease compared to the general population in Poland – a comparative analysis

IntroductionEnd-stage renal disease (ESRD) is an important complication of diabetes, which is the leading cause of ESRD worldwide. The aim of the study was a comparative analysis of all-cause mortality in patients with ESRD with diagnosed diabetes mellitus (DM) and no diagnosed DM.Material and methodsData for the analysis were obtained from the resources of the Polish National Health Fund, and they concerned patients with end-stage renal disease from the entire population of Polish patients in the period from 1.01.2011 to 31.12.2013. In addition, the period from 1.01.2012 to 31.12.2012 was analysed for two subpopulations: diabetic and non-diabetic patients.ResultsThe all-cause mortality in patients with end-stage renal disease in Poland per 100,000 representatives of the general population was 17.7, 15.9, and 12.50 persons in 2011, 2012, and 2013, respectively. The all-cause mortality rates for patients with ESRD and diabetes in Poland in 2012 were more than 15 times higher, for both men and women, than the all-cause mortality rates for non-diabetic patients with ESRD. Mortality in the study group of diabetic men with ESRD amounted to 147.59 ±29.07/100,000 men, whereas in the study group of diabetic women with ESRD it was 105.13 ±26.77/100,000 women. Regarding non-diabetic men with ESRD and non-diabetic women with ESRD, mortality amounted to 9.58 ±6.29/100,000 and 6.87 ±2.27/100,000 men and women, respectively.ConclusionsThe occurrence of diabetes in patients with ESRD significantly increases the risk of death compared to patients with ESRD without diabetes.

Niveles séricos de 25-Hidroxivitamina D y su relación con síndrome metabólico en una población de hombres jóvenes no diabéticos.

Introducción: Los niveles no suficientes de vitamina D (VD) se han asociado a varias patologías no osteomusculares, sin embargo, es motivo de controversia si estos se asocian a mayor prevalencia de síndrome metabólico (SM).&#x0D; Objetivo: Determinar y comparar la frecuencia de insuficiencia y deficiencia de 25-Hidroxivitamina D (25(OH)D) entre hombres jóvenes obesos no diabéticos y controles con peso normal, y su correlación con el estado de síndrome metabólico.&#x0D; Materiales y métodos: Estudio de corte transversal, que incluyó 62 individuos con peso normal y 47 en obesidad, se determinaron los niveles séricos de 25(OH)D. y se midieron parámetros antropométricos y bioquímicos para establecer criterios de SM.&#x0D; Resultados: De los 47 sujetos con obesidad, 25 tenían SM, mientas que ninguno de los sujetos de peso normal cumplía con dichos criterios, No se encontraron diferencias estadísticamente significativas en cuanto a la presencia de síndrome en correlación con los niveles de vitamina D (p=0,94).. La media de los niveles séricos de 25(OH)D para la población total fue de 30,64 ng/mL; en sujetos normopeso 30,8 ng/mL y entre los obesos fue de 30,1 ng/mL con SM y 30,6 ng/mL. Por otro lado no hubo una correlación significativa entre los parámetros individuales de síndrome metabólico y los niveles séricos de VD tanto de manera global como en el análisis por subgrupos.&#x0D; Conclusión: No hubo una correlación significativa entre los niveles séricos de 25(OH)D con el estado de SM, tampoco se identificó ningún tipo de correlación significativa entre estos y los parámetros antropométricos y bioquímicos estudiados.

Plasma biomarkers of small intestine adaptations in obesity-related metabolic alterations

BackgroundEvidence suggests that pathophysiological conditions such as obesity and type 2 diabetes (T2D) are associated with morphologic and metabolic alterations in the small intestinal mucosa. Exploring these alterations generally requires invasive methods, limiting data acquisition to subjects with enteropathies or undergoing bariatric surgery. We aimed to evaluate small intestine epithelial cell homeostasis in a cohort of men covering a wide range of adiposity and glucose homoeostasis statuses.MethodsPlasma levels of citrulline, a biomarker of enterocyte mass, and I-FABP, a biomarker of enterocyte death, were measured by UHPLC‑MS and ELISA in 154 nondiabetic men and 67 men with a T2D diagnosis.ResultsPlasma citrulline was significantly reduced in men with insulin resistance and T2D compared to insulin sensitive men. Decreased citrulline levels were, however, not observed in men with uncontrolled metabolic parameters during T2D. Plasma I-FABP was significantly higher in men with T2D, especially in presence of uncontrolled glycemic and lipid profile parameters. Integration of both parameters, which estimate enterocyte turnover, was associated with glucose homeostasis as well as with T2D diagnosis. Differences in biomarkers levels were independent of age and BMI and glucose filtration rates.ConclusionsOur study supports a decreased functional enterocyte mass and an increased enterocyte death rate in presence of metabolic alterations but emphasizes that epithelial cell homeostasis is especially altered in presence of severe insulin resistance and T2D. The marked changes in small intestine cellularity observed in obesity and diabetes are thus suggested to be part of gut dysfunctions, mainly at an advanced stage of the disease.

MP84-13 LIRAGLUTIDE AMELIORATES ERECTILE DYSFUNCTION VIA REGULATING AUTOPHAGY AND RHOA/ROCK PATHWAY INDUCED BY OXIDATIVE STRESS IN DIABETES MELLITUS

INTRODUCTION AND OBJECTIVE:As one of diabetic complications, erectile dysfunction (ED) is more frequent and causes worse response to PDE5 inhibitors compared with non-diabetic men. Corpus cavernosu...

Elevated Fasting Blood Glucose Levels Are Associated With Lower Cognitive Function, With a Threshold in Non-Diabetic Individuals: A Population-Based Study.

BackgroundCognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals.MethodsParticipants were Japanese diabetic (n = 191) and non-diabetic (n = 616) men, aged 46–81 years, from 2010–2014. Blood samples were taken after a 12 h fast. The Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score.ResultsFor diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66–0.12) lower per 1 mmol/L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse U-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97–6.20 mmol/L (71.5–111.6 mg/dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose.ConclusionsElevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain among non-diabetic men.

Rationale and protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes

BackgroundIntermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study (Daily versus Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. MethodsAnticipated 260 non-diabetic men and women aged 35–75 years, BMI 25−50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. DiscussionThis study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes.

Twelve weeks of exenatide treatment increases [18F]fluorodeoxyglucose uptake by brown adipose tissue without affecting oxidative resting energy expenditure in nondiabetic males

Aims/hypothesisBrown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes. MethodsTwelve Dutch South Asian and 12 age- and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [18F]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale. ResultsSince the effect of exenatide on metabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased body weight (−1.5 ± 0.4 kg, p < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (−15%, p < 0.05) and total cholesterol (−5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([18F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). Conclusions/interpretationWe show for the first time that GLP-1R agonism increases [18F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. Trial registryClinicaltrials.gov NCT03002675.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099–1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107–1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Relationship between Obesity Indicators and Gingival Inflammation in Middle-aged Japanese Men.

The purpose of this study was to investigate the relationship among the waist-to-height ratio (WHtR) and the body mass index (BMI) as obesity indicators and gingival inflammation as determined by bleeding on probing (BOP). The participants comprised employees of a milk products company based in Tokyo, Japan. A total of 159 non-diabetic men aged 40 to 59 yr and with a minimum of 28 teeth were included. Multiple logistic regression analysis controlling for age, smoking status, pocket depth, frequency of daily brushing, frequency of weekly interdental brushing, and regular dental attendance was performed to compare the relationships among the obesity indicators and BOP. Participants with good oral hygiene had significantly less BOP than those with poor oral hygiene (p<0.001). No significant differences were observed among the other items investigated. A significant association was observed between WHtR and BOP (odds ratio: 2.40, 95% confidence interval: 1.11-5.22); no such association was observed with the BMI, however. The present results showed that obesity, as determined according to a visceral fat index, was associated with BOP, but not with BMI. This suggests that the WHtR is a more accurate index of obesity than the BMI in studies on BOP.