Prediabetic Participants Research Articles

Oxygen-18 and carbon-13 isotopes in eCO2 and erythrocytes carbonic anhydrase activity of Finnish prediabetic population

Complex human physiological processes create the stable isotopic composition of exhaled carbon dioxide (eCO2), measurable with noninvasive breath tests. Recently, isotope-selective breath tests utilizing natural fluctuation in 18O/16O isotope ratio in eCO2 have been proposed for screening prediabetic (PD) individuals. It has been suggested that 18O/16O fractionation patterns reflect shifts in the activity of carbonic anhydrase (CA), an enzyme involved in the metabolic changes in the PD state. To evaluate the applicability of the breath sampling method in Finnish PD individuals, breath delta values (BDVs, ‰) of 18O/16O (δ 18O) were monitored for 120 min in real-time with a high-precision optical isotope ratio spectrometer, both in the fasting state and during a 2 h oral glucose tolerance test (2 h OGTT) with non-labeled glucose. In addition, the BDV of 13C/12C (δ 13C) was measured, and total erythrocyte CA activity was determined. δ 18O and CA did not demonstrate any statistically significant differences between PD and non-diabetic control (NDC) participants. Instead, δ 13C was significantly lower in PD patients in comparison to NDCs in the fasting state and at time points 90 and 120 min of the 2 h OGTT, thus indicating slightly better potential in identifying Finnish PD individuals. However, overlapping values were measured in PD participants and NDCs, and therefore, δ 13C cannot be applied as a sole measure in screening prediabetes at an individual level. Thus, because the combination of environmental and lifestyle factors and anthropometric parameters has a greater effect on glucose metabolism and CA activity in comparison to the PD state, 18O/16O and 13C/12C fractionations or CA activity did not prove to be reliable biomarkers for impaired glucose tolerance in Finnish subjects.This study was conducted under the clinicaltrials.gov ID NCT03156478.

Proinsulin-specific T-cell responses correlate with estimated c-peptide and predict partial remission duration in type 1 diabetes.

ObjectiveType 1 diabetes (T1D) is an autoimmune disorder in which autoreactive T cells destroy insulin‐producing β‐cells. Interventions that preserve β‐cell function represent a fundamental therapeutic goal in T1D and biomarkers that predict and monitor β‐cell function, and changes in islet autoantigenic signatures are needed. As proinsulin and neoantigens derived from proinsulin peptides (hybrid insulin peptides, HIPs) are important T1D autoantigens, we analysed peripheral blood CD4+ T‐cell autoantigen‐specific proliferative responses and their relationship to estimated β‐cell function.MethodsWe recruited 72 people with and 42 without T1D, including 17 pre‐diabetic islet antibody‐positive and 9 antibody‐negative first‐degree relatives and 16 unrelated healthy controls with T1D‐risk HLA types. We estimated C‐peptide level at 3‐month intervals for 2 years post‐diagnosis and measured CD4+ T‐cell proliferation to proinsulin epitopes and HIPs using an optimised bioassay.ResultsWe show that CD4+ T‐cell proliferation to any islet peptide and to multiple epitopes were significantly more frequent in pre‐diabetic islet antibody‐positive siblings and participants with T1D ≤ 3 months of duration, than in participants with T1D > 3 months or healthy controls. Among participants with T1D and first‐degree relatives, CD4+ T‐cell proliferation occurred most frequently in response to proinsulin33‐63 (full‐length C‐peptide). Proinsulin33‐63‐specific responses were associated with HLA‐DR3‐DQ2 and/or HLA‐DR4/DQ8. In children with T1D, proinsulin33‐63‐specific T‐cell proliferation positively associated with concurrent estimated C‐peptide and predicted survival in honeymoon.ConclusionCD4+ T‐cell proliferative responses to proinsulin‐containing autoantigens are common before and immediately after diagnosis of T1D but decline thereafter. Proinsulin33‐63‐specific CD4+ T‐cell response is a novel marker of estimated residual endogenous β‐cell function and predicts a better 2‐year disease outcome.

Visceral adiposity index is closely associated with urinary albumin‐creatinine ratio in the Chinese population with prediabetes

Visceral obesity is a major health issue and is a risk factor for an atherogenic state. Visceral obesity has been reported to be a crucial link between albuminuria and cardiovascular diseases (CVD). This study attempted to explore the association between visceral obesity and albuminuria in prediabetic individuals. This cross-sectional study included 24871 prediabetic participants over 40 years of age from seven centres across China (REACTION study). The visceral adiposity index (VAI) was determined based on the measurements of anthropometric indices and lipid parameters. Increased albuminuria was defined as a urinary albumin-creatinine ratio (UACR) ≥30 mg/g, indicating kidney damage. Propensity score matching was used to reduce bias, and a multiple logistic regression model was performed to evaluate the association between visceral obesity and albuminuria in the population with prediabetes. Participants with increased UACR exhibited increased VAI, age, blood pressure, triglycerides, poor glycaemic control, CVD events, and decreased estimated glomerular filtration rate (eGFR). Multiple logistic regression analysis demonstrated that VAI quartiles were positively associated with an increased risk of albuminuria (Q2: odds rate [OR]: 1.10, 95% confidence intervals [CI] 0.96-1.25; Q3: OR: 1.16, 95% CI 1.01-1.32; Q4: OR: 1.26, 95% CI 1.10-1.44, p for trend=0.001). Stratified analysis revealed that the association of VAI level with increased albuminuria risk also occurred in people who were young, women, overweight or obese, with poor control of blood pressure, and eGFR ≥90 ml/min per 1.73 m2 . Visceral obesity assessed by VAI is significantly associated with increased UACR in a Chinese population with prediabetes.

Metabolomic signatures for visceral adiposity and dysglycaemia in Asian Chinese and Caucasian European adults: the cross-sectional TOFI_Asia study

BackgroundAsian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes.MethodsFasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography–mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBF and clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests.ResultsFPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29, p = 3.00E−05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28, p = 2.02E−07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBF was correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3, p = 8.25E−09) in Caucasians and TG(58:3) (adjusted β = 0.25, p = 2.34E−08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBF were common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities.ConclusionsUntargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.

Acute Vs. Chronic Responses To Exercise Training In Type-2 Vs. Pre-diabetic Adults.

Exercise is recommended for improving glycemic control yet it remains unclear whether exercise training produces similar acute and chronic adaptations in T2DM vs. pre-diabetic individuals given their varying states of insulin resistance. PURPOSE: To compare acute and chronic exercise training adaptations in response to the same exercise training program in T2DM vs. pre-diabetic individuals. METHODS 18 male (n=8) and female (n=10), previously inactive (no planned physical activity), adults with T2DM (n=10) or pre-diabetes (n=8) completed the same exercise training program (3 days/wk, 8 wks). Before and exactly 72-hr after participants’ last exercise session, chronic adaptations in body fat percentage ([BF%] assessed via dual x-ray absorptiometry), fitness determined by a 6-minute walk test, resting systolic (SBP) and diastolic (DBP) blood pressure, fasting blood glucose (BG), and self-efficacy using the Self-Efficacy for Exercise Scale (SEE) were measured. Participants’ SBP, DBP, and BG were also monitored immediately before and 5-min after each exercise session to determine acute responses to exercise. RESULTS: A significant improvement in 6MWT was observed for T2DM (1544 ± 82 vs. 1752 ± 80 ft., p<0.01) and pre-diabetic (1414 ± 97 vs. 1624 ± 115 ft., p<0.01) participants. No significant chronic or acute changes were observed in SBP for either group. A significant improvement in resting DBP was observed in T2DM (80 ± 2 vs. 75 ± 3 mmHg, p=0.03) but not pre-diabetic (75 ± 2 vs. 79 ± 3 mmHg, p=0.13) participants yet no acute changes were observed in DBP for either group. No significant changes were observed in fasting BG in either group. Acutely exercise resulted in significantly lower BG in diabetic (172 ± 12 vs. 145 ± 11 mg/dL, p<0.01) and pre-diabetic (104 ± 4 vs. 95 ± 3 mg/dL, p<0.01) participants. A significant improvement in SEE was observed in diabetic (34.3 ± 9.0 vs. 65.0 ± 9.0, p=0.029), but not pre-diabetic (38.8 ±12.8 vs. 60.0 ± 12.8, p=0.24) participants. CONCLUSION: Despite varying states of insulin resistance, exercise training resulted in similar improvements in fitness and acute improvements in blood glucose in both diabetic and pre-diabetic adults. However, unlike pre-diabetics, diabetic participants experienced additional benefits in resting diastolic blood pressure and exercise self-efficacy.

P74 A Community-Based Intervention Reduces Diabetes Risk in a Low-Income Community

<h3>Objective</h3> Promote diabetes prevention in a low-income community by offering Cooking Matters (CM) in coordination with the Diabetes Prevention Program (DPP). <h3>Use of Theory or Research</h3> Reducing food insecurity is important for reducing chronic disease rates. DPP is a validated and effective intervention that reduces progression to type 2 diabetes. However, there is an outcome disparity for DPP in low-income communities. Our research aims to improve DPP outcomes in low-income communities. <h3>Target Audience</h3> Pre-diabetic participants ≥18 years old in low-income communities in Detroit, Michigan. <h3>Program Description</h3> This study represents partnerships between Gleaners Community Food Bank (GCFB), National Kidney Foundation of Michigan (NKFM), and Wayne State University. DPP, administered by NKFM, is a community-based intervention that significantly reduces diabetes risk. CM, locally administered through GCFB, is another effective community program that teaches food skills, and provides food provisions. We hypothesize that combining DPP and CM in a low-income setting will improve program completion, and thereby reduce the risks for progressing to type 2 diabetes. <h3>Evaluation Methods</h3> Over 12 months, low-income individuals participated in the study. Demographics were collected at the onset of the study. Survey information was collected for diet and physical activity at 4 time-points throughout the study. Body weight was collected at every session, and HbA1C was collected at the onset and conclusion of the program. <h3>Results</h3> Combining DPP and CM resulted in a 79% completion rate, compared to the <50% completion rate observed for DPP alone in low-income communities. Mean HbA1C dropped 10.6% (paired t-test, <i>P</i> < .01), from pre-diabetic to normal levels, and every participant demonstrated lower post-test HbA1C values. Participants experienced a mean weight loss of 7.6% (paired t-test, <i>P</i> < .01), and >75% of participants exceeded 5% weight loss at 12 months. <h3>Conclusions</h3> Combining DPP and CM is effective at reducing diabetes risk in low-income communities. Food bank services, which already serve low-income vulnerable communities, can be coupled to existing chronic illness prevention programs to improve disease risk in vulnerable populations.

73-LB: Expanding the Definition of Intraday Glucose Variability

Glucose variability (GV) is an established risk factor for hypoglycemia and diabetes complications. Over 20 GV metrics have been identified, but there is no consensus on which metrics are most effective for determining glucose control. A1c is the clinical standard of glucose control. Two of the most common GV metrics include intraday standard deviation (iSD) and intraday coefficient of variation (iCV), which are calculated for each day and then averaged over multiple days. Thus, the current metrics of iSD and iCV are aggregate means, which are influenced by outliers and do not consider variations over multiple days. To reduce the influence of outliers and examine variation in these metrics over multiple days, we propose expanding the definition of iSD and iCV to include median and standard deviation of iSD and iCV over multiple days. We examined iSD and iCV in a population of 14 high normoglycemic or prediabetic participants (A1c 5.5-6.4%). Participants wore a continuous glucose monitor for 8-10 days. In addition to iSD and iCV, 23 metrics of glucose and GV were calculated. To determine the strength of the relationship between each GV metric and A1c, Pearson correlation coefficients (PCC) were calculated. There were higher PCC between A1c and the standard deviation of iSD and iCV than the traditional metric of iSD and iCV (traditional: 0.296, SD: -0.387). Interestingly, all metrics of iSD and iCV calculated (mean, median, and standard deviation) were more closely correlated with A1c than mean glucose (0.296, 0.138, -0.387, and 0.220, respectively). We demonstrate that expanding the definitions of iSD and iCV can provide a more comprehensive view of GV. Additionally, these metrics may provide more insight into glucose control than traditionally utilized metric, mean glucose. Disclosure P.J. Cho: None. B.M. Bent: None. A.H. Wittmann: None. R.M. Merwin: None. C.R. Thacker: None. M.N. Feinglos: None. J.P. Dunn: None. Funding MEDx (451-1746)

Plasma concentrations of vitamin A and E and risk of dysglycemia in first-trimester pregnant Saudi women

BackgroundExisting evidence suggest that low concentrations of vitamin A and E may have a contribution to the development of diabetes complications; however, data regarding the status of vitamin A and E among individuals with prediabetes are lacking. This study aimed to examine the association of plasma concentrations of vitamin A and E with the glycemic control status among first trimester pregnant Saudi women.MethodsIn this cross-sectional study, 1102 first trimester pregnant Saudi women were recruited from antenatal clinics. Sociodemographic and anthropometric information were collected, and laboratory analyses of blood glycated hemoglobin (A1C) and plasma vitamins A and E were performed. Subjects were classified as normoglycemic, prediabetic, or undiagnosed diabetic. Multinomial regression models adjusted for age estimated the adjusted odds ratios (aORs) and [95% confidence intervals (CIs)].ResultsAmong the sample, 78.8% (n = 868) had normal glycemic control, while 19.1% (n = 211) had prediabetes and 2.1% (n = 23) had undiagnosed diabetes. Plasma concentrations of vitamin A and E of prediabetic participants were at a level midway between that of normoglycemic and diabetic participants (p < 0.01). Compared to subjects with normoglycemic status, those with higher concentrations of vitamin A and E had lower odds of being prediabetic (aOR = 0.27 [0.21–0.35] and aOR = 0.95 [0.94–0.96], respectively) or diabetic (aOR = 0.18 [0.13–0.24] and aOR = 0.93 [0.92–0.94], respectively).ConclusionsOur findings indicate a possible contribution of vitamins A and E to the progression of prediabetes to diabetes. Future longitudinal studies are needed to elucidate the association between the antioxidant status and dysglycemia. Clinicians should monitor the glycemic and the antioxidant status closely and provide dietary guidance where needed.

Effect of different doses of Moringa oleifera in postprandial glucose. Influence of participants’ glucose control status

AbstractThe multipurpose plant Moringa oleifera (MO) has shown a variety of in vitro activities potentially beneficial for health and evidences are also numerous in animal models. However, the exact composition of the plant is highly variable depending on the area, culture and post harvesting conditions and the effects in humans are scarcely studied. This is a pilot study of the effect of different doses of MO from an Iberian Peninsula cultivar on postprandial glucose level in non-diabetic subjects. Five adult subjects (40 to 70 years, 3 males) with normal renal and hepatic function were included. Two had normal fasting glucose and 3 had pre-diabetic fasting glucose. A standard breakfast plus, respectively, one placebo capsule (PLC), or 1, 3 and 6 capsules containing 400 mg of MO dry leaf powder (MO-1cap, -3cap and -6cap) were consumed by each subject on 4 consecutive visits, one week apart. The basal and postprandial (30, 60, 90, 120, 150 and 180 min) glucose was measured. The mean glucose change from baseline (ΔGlc) at each measure time was calculated and compared between treatments with the Wilcoxon tests and considered significant at P &lt; 0.05 level. The postprandial curves were also studied separately in pre-diabetic subjects. A difference was found 90 min after breakfast in ΔGlc for the MO-6cap compared to the MO-1cap, being lower in MO-6cap. No more significant differences were observed due to the small number of subjects and high variability in glucose values among subjects. However, the graphical representation of separated curves for the three pre-diabetic participants showed that all three MO doses led to values always below those with PLC. In addition, during the first experimental hour all MO doses showed lower ΔGlc than PLC while this was not the case when all subjects were studied. No adverse events occurred during the experiment. The study, thus, showed a trend to lower glycemic postprandial response with MO leaf powder which seems to be more evident in pre-diabetic subjects than in normoglycemic subjects and especially during the first postprandial hour. The MO-6cap seems to be the election daily dose for a long term intervention study on the glycemic control with MO in pre-diabetic subjects.

Outcomes of a Weight Loss Intervention to Prevent Diabetes Among Low-Income Residents of East Harlem, New York.

There is a need for diabetes prevention efforts targeting vulnerable populations. Our community-academic partnership, the East Harlem Partnership for Diabetes Prevention, conducted a randomized controlled trial to study the impact of peer led diabetes prevention workshops on weight and diabetes risk among an economically and racially diverse population in East Harlem, New York. We recruited overweight/obese adults from more than 50 community sites and conducted oral glucose tolerance testing and completed other clinical assessments and a health and lifestyle survey. We randomized prediabetic participants to intervention or delayed intervention groups. Intervention participants attended eight 90-minute peer-led workshop sessions at community sites. Participants in both groups returned for follow-up assessments 6 months after randomization. The main outcomes were the proportion of participants who achieved 5% weight loss, percentage weight loss, and change in the probability of developing diabetes over the next 7.5 years according to the San Antonio Diabetes Prediction Model. We enrolled 402 participants who were mainly female (85%), Latino (73%) or Black (23%), foreign born (64%), and non-English speaking (58%). At 6 months, the intervention group lost a greater percentage of their baseline weight, had significantly lower rise in HbA1c (glycated hemoglobin), decreased risk of diabetes, larger decreases in fat and fiber intake, improved confidence in nutrition label reading, and decrease in sedentary behavior as compared with the control group. Thus, in partnership with community stakeholders, we created an effective low-resource program that was less intensive than previously studied programs by incorporating strategies to engage and affect our priority population.

Prevalence of Prediabetes, Diabetes and Its Predictors among Females in Alkharj, Saudi Arabia: A Cross-Sectional Study.

Background/Objective:The prevalence of prediabetes and diabetes is reaching epidemic proportions across the globe. Therefore, this study aims to determine the prevalence of prediabetes and diabetes, together with its accompanying risk factors, among young females.Methods:An exploratory cross-sectional survey was conducted with 638 Saudi females in Alkharj, Saudi Arabia. Statistical analysis was carried out using STATA version 14. Odds ratios for the risk of diabetes and associated factors were calculated using log-binomial and multinomial logistic regression. Standardized prevalence and strata-specific prevalence of diabetes and prediabetes for different risk factors were also calculated.Findings:The study revealed that nondiabetics and prediabetics were more prevalent between the ages of 18 and 24 years, while diabetic patients were consistently between 25 to 44 years of age. The average value for HbA1c in females was 5.44. Regression analysis shows that being older, married, obese, a smoker or less educated significantly increases the risk for both prediabetes and diabetes. Mutivariable analysis revealed obesity had a significant association with both prediabetes and diabetes. Prediabetics were 2.35 times more likely to be obese as compared to nondiabetics, with 95% CI (1.38–3.99). Similarly, diabetics were 6.67 times more likely to be obese compared to nondiabetics 95% CI (1.68–26.42).Conclusion:Our study shows the prevalence of diabetes and prediabetes among females from Al Kharj was 3.8% and 18.8%, respectively. The diabetic and prediabetic female participants had higher mean BMI and waist circumference, were older in age, were married, and smoked as compared to nondiabetics. In the context of the findings of our study, and keeping in view the the burden of this disease globally and in our population, it has now become extremely important to understand these factors and encourage health-promoting behaviors to construct effective interventions.

1504-P: Low Normal Free Thyroxine Levels Are Associated with Prediabetes in Euthyroid Subjects

Background: Although the association between low-normal thyroid function and metabolic syndrome was well documented, little is known about the effect of thyroid hormone within the physiological range on carbohydrate metabolism. This study aimed to determine whether free thyroxine (FT4) influences serum glucose concentration and the prevalence of prediabetes in euthyroid subjects. Methods: This was a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 4,767 participants of &amp;gt;20 years of age who were euthyroid and nondiabetic. Results: Prediabetic participants had lower FT4 concentrations than those without prediabetes, but thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, HbA1c levels significantly decreased with FT4 tertile, whereas FBG was not associated with FT4 both in men and in women. The prevalence of prediabetes was significantly higher in T1 than in T3. Conclusion: Subjects with low-normal serum FT4 had high HbA1c and were more likely to have the prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes, even though thyroid function is within the normal range. Thus, screening for prediabetes in subjects with low-normal FT4 should involve the measurement of HbA1c. Disclosure S. Kim: None. E. Jeon: None. J. Lee: None. H. Shon: None. K. Park: None.

Effects of Cinnamon Spice on Postprandial Plasma Levels of Glucose and Insulin in Healthy Participant with Normal Weight (FS15-04-19)

ObjectivesThe objective of this study is to investigate the effect of one time intake of cinnamon spice on the postprandial glucose tolerance and insulin secretion following consumption of a high glycemic index meal in normal weight and glucose tolerance individuals. MethodsSixteen healthy controls (BMI = 18.5–24.9 kg/m2 and fasting blood glucose (BG) < 100 mg/dL) aging 20–50 years, who typically consume a low fiber/polyphenol diet (beige diet) were recruited for this study. Recruitment of overweight/obese, prediabetic participants is not completed (no data presented). Participants consume a typical American breakfast containing 50 g of carbohydrates (1/3 cup of oatmeal and 1 cup 2% milk) with or without cinnamon (6 g) followed by 1-week washout and crossover to the opposite intervention. The blood samples were taken at fasting state and at 30, 60, 90, 120, 150 and 180 minutes after the meal. The main outcome measures included BG and insulin. The secondary outcome measures were C-peptide and glucagon. Cinnamon spice (Indonesia) was purchased at the local grocery store (McCormick®) and contains 3.9% proanthocyanin. The statistical significance was set at P < 0.05 using SPSS. ResultsConsumingcinnamon spice with the oatmeal significantly decreased the rate of glucose change from fasting state at 60 and 90 minutes after the meal by 37% and 31%, respectively. The peak postprandial BG and the areas under the curve (AUC) of glucose were also lowered by cinnamon compared to oatmeal alone but did not reach the significant levels. There was a trend towards significant decrease (21%, P = 0.08) in plasma insulin concentrations and a significant decrease in plasma C-peptide levels 30 minutes after ingestion of the meal with cinnamon. Cinnamon ingestion compared to oatmeal alone also significantly decreased plasma glucagon levels at 90 minutes after the meal test. ConclusionsOur results suggest that one time intake of cinnamon spice lowers the mean rate of glucose change following a high glycemic index meal in healthy individuals. Cinnamon also decreased plasma levels of insulin, C-peptide, and glucagon. Funding SourcesUCLA Center for Human Nutrition.

244-LB: Glutamate Is Associated with Type 2 Diabetes through PLG Regulation

Glutamate is a major excitatory neurotransmitter and is involved in the ER stress and β-cell dysfunction, which are important clinical features of diabetes mellitus. However, metabolic studies of diabetes in relation to glutamate are not well understood. In this regard, we tried to search for the function of glutamate in type 2 diabetes. We found that glutamate levels were significantly increased in both prediabetic and diabetic participants in 10 years follow-up study (Korean Genome and Epidemiology Study: Ansan-Ansung cohort). And also, we observed that glutamate is associated with FERM domain-containing protein 4B (FRMD4B), plasminogen (PLG) and partitioning-defective 3 (PARD3) by genome-wide association studies (GWAS). Among them, PLG levels were not only significantly increased by palmitate treatment, which is general model for induction of insulin resistance, but also increased by glutamate treatment. To demonstrate the association between PLG and type 2 diabetes, we treated thapsigargin (ER stress) or oligomysin (mitochondrial dysfunction) in Sk-Hep I cells, and observed that PLG levels were significantly increased in these conditions. Consistently, PLG overexpression increased expression of ER stress-related factors; however, repression of PLG expression by plg siRNA attenuated these changes. Our results demonstrate that high levels of glutamate are associated with development of diabetes, and are assumedly regulated by PLG. Disclosure H. Lee: None. J. Yun: None. H. Kim: None. H. Jang: None. S. Park: None. H. Lee: None. Funding Korea National Institute of Health (2017-NG64001-02)

Fruit in Diets for Diabetes (P08-086-19)

ObjectivesDetermine the effect on glycemic response of equi-carbohydrate partial exchange of fruit for cereal, identify mechanisms of its effectiveness, and establish the metabolic safety of long-term fruit consumption in individuals at risk of type 2 diabetes. MethodsRandomised repeated measures human intervention studies were conducted with healthy participants ingesting 40 g available carbohydrate meals of wheaten starch biscuit (WB), WB plus kiwifruit (WB + KF), and WB plus the same sugars in the same quantity as consumed in the kiwifruit (WB + KFS). Postprandial glycemic responses were measured.Associated in vitro studies aimed to identify mechanisms of glycemic response reduction by fruit. Physicochemical and rheological properties of fruit digested under simulated gastro-intestinal conditions, and the impact of the fruit remnants on physical and enzymatic processes of digestion were determined.In a follow-up parallel group intervention study, prediabetic (HBA1c > 4%) participants consumed 2 kiwifruit per day for 12 weeks, to establish the metabolic safety of long term kiwifruit consumption through clinical biomarkers. ResultsPartial substitution by kiwifruit (WB + KF) significantly (P < 0.05) and substantially (−35%) reduced glycemic response peak height compared with unsubstituted WB. Also, substitution by kiwifruit (WB + KF) caused significantly (P < 0.001) lower (−20%) peak glycaemic response than substitution with the kiwifruit sugars alone (WB + KFS), indicating the glycemia reducing effect of the fruit was due to more than fructose substitution of digestible starch. The mechanistic studies showed several gut-level factors by which kiwifruit could reduce glycemic impact; high gastric acidification and buffering capacity, swelling and dispersion of the fruit cell walls (dietary fiber) leading to rheological changes retarding digestion, glucose diffusion and intraluminal mixing, all involved in transport of digestion products to the gut wall for absorption. The long term study could not detect adverse metabolic effects. ConclusionsIncluding fruit in the diet in a carbohydrate exchange format may suppress glycemic response through a number of mechanisms and without metabolic risk. Funding SourcesNew Zealand National Science Challenge.

Perception on food exchange system and its influential factors in the pre-diabetes population in the community

Objective To investigate the pre-diabetic people's perception towards food exchange system in the community, and to analyze the influential factors of the perception, in order to provide guidance for the wide use of the system. Methods By cluster sampling, 598 pre-diabetic participants who attended to 4 community health service centers in Chaoyang District in Beijing during the period of July to December 2016 were selected to participate in a questionnaire survey. Their perception on the food exchange system was analyzed and influential factors were analyzed by Logistic regression. Results Among the participants, 191 of them could accurately perceive the system, which accounted for 31.94%; 49 participants often used the system, accounting for 25.65%; 142 participants knew how to use the system but seldom used it and it counted for 74.35%; 407 participants had no knowledge about the system and that accounted for 68.06%. In terms of the awareness rate, females and abdominal obese group were greater than males and non-abdominal obese group with statistically significant differences (χ2=15.42, 27.72; P<0.01) . Logistic regression analysis indicated that abdominal obesity was the influential factor for the pre-diabetic participants in regards to their perception towards the food exchange system. Conclusions In the pre-diabetic participants, abdominal obesity is an influential factor affecting the low awareness rate towards the food exchange system. It is recommended that various forms of health education through various ways should be conducted for the population to improve their awareness and knowledge towards the system and hence to reduce the risk of developing into diabetes ultimately. Key words: Community health nursing; Prediabetic state; Food exchange system; Influential factors

Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD Study) \u2013 study protocol for a randomised placebo-controlled trial in Australia

BackgroundDiabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia.Methods/designThe study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7–6.4) male and female participants (n = 410) aged 40–70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months.DiscussionThis study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes.Trial registrationAustralian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

Ayurvedic polyherbal combination (PDBT) for prediabetes: A randomized double blind placebo controlled study

BackgroundIncreasing prevalence of type 2 diabetes mellitus (DM) has become alarming, burdening health care systems throughout the world. Prediabetes is an intermediate step before manifestation of full blown DM. Effective intervention at this step would help stop/slow progression to DM. ObjectiveThis study aimed at use of a polyherbal combination (PDBT – constituted of Tinospora cordifolia, Pterocarpus marsupium, Gymnema sylvestre, Zingiber officinale and Momordica charantia) along with life style modification compared to a placebo in prevention of DM among prediabetic individuals. Materials and MethodsThe study was a double blinded, placebo controlled randomized clinical trial. Participants were divided in to a group on PDBT and life style management (LSM) and second on placebo and LSM. Participants in the intervention group received 2 gm/day of PDBT. All participants received the intervention for a period of 6 months. ResultsOne hundred and fourteen participants were enrolled in the study, 57 each in intervention and control group. At the end of the study, 8 participants from the intervention group, compared to 15 participants in the control group had converted to DM. There was a 47% risk reduction in the intervention group. Participants in the intervention group showed statistically significant decrease in their blood glucose level (fasting and PP), HbA1c, fasting serum insulin and HOMA-IR values. There was no significant change in BMI. No adverse effects were reported by any participants. ConclusionPDBT along with LSM in prediabetic participants was associated with reduction in conversion to DM than placebo along with LSM without any adverse effects.

Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes.

Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Demographic and Social-Cognitive Factors Associated with Weight Loss in Overweight, Pre-diabetic Participants of the PREVIEW Study

PurposeWeight loss has been demonstrated to be a successful strategy in diabetes prevention. Although weight loss is greatly influenced by dietary behaviors, social-cognitive factors play an important role in behavioral determination. This study aimed to identify demographic and social-cognitive factors (intention, self-efficacy, outcome expectancies, social support, and motivation with regard to dietary behavior and goal adjustment) associated with weight loss in overweight and obese participants from the PREVIEW study who had pre-diabetes.MethodProspective correlational data from 1973 adult participants were analyzed. The participants completed psychological questionnaires that assessed social-cognitive variables with regard to dietary behavior. Stepwise multiple regression analyses were performed to identify baseline demographic and social-cognitive factors associated with weight loss.ResultsOverall, being male, having a higher baseline BMI, having a higher income, perceiving fewer disadvantages of a healthy diet (outcome expectancies), experiencing less discouragement for healthy eating by family and friends (social support), and lower education were independently linked to greater weight loss. When evaluating females and males separately, education was no longer associated with weight loss.ConclusionThe results indicate that a supportive environment in which family members and friends avoid discouraging healthy eating, with the application of a strategy that uses specific behavior change techniques to emphasize the benefits of outcomes, i.e., the benefits of a healthy diet, may support weight loss efforts. Weight loss programs should therefore always address the social environment of persons who try to lose body weight because family members and friends can be important supporters in reaching a weight loss goal.