2-hour Glucose Levels Research Articles

Acarbose versus Repaglinide in Diabetes Treatment: A New Appraisal of Two Old Rivals

BackgroundAcarbose and repaglinide are two safe and effective antidiabetic agents that are especially in wide use in Asian and Middle Eastern countries. These two prandial agents share some outstanding qualities that their newer counterparts do not. While globally available in generic versions, both are oral and cheap. There is a paucity of data regarding their comparative efficacy. Herein, a head-to-head comparison of the efficacy of the two in treatment of postprandial hyperglycemia of newly-diagnosed type 2 diabetes was investigated. Materials and MethodsOne hundred and sixty-four newly-diagnosed type 2 diabetes patients with fasting plasma glucose levels of <7.2 mmol/L (130 mg/dL) but 2-hour postprandial glucose (2hPPG) levels of >10 mmol/L (180 mg/dL) were consecutively alternated between acarbose- and repaglinide-treatment for 6 months. ResultsPer protocol analysis, 67% of acarbose-treated patients versus 85% of repaglinide-treated patients achieved 2hPPG levels of <10 mmol/L (180 mg/dL) (P = 0.05). Treatment adherence rates were 52.4% and 72%, respectively (P < 0.02). Thirteen of the repaglinide-treated and 2 of acarbose-treated patients reported at least one episode of hypoglycemia (P < 0.03). Fasting plasma glucose, 2hPPG, glycated hemoglobin and basal insulin requirement decreased more significantly with repaglinde than acarbose (P, <0.05, <0.04, <0.04 and <0.03, respectively). Weight increased with repaglinide and decreased with acarbose (P = 0.03). There were no significant changes in LDL levels with either treatment (P = 0.58), but triglycerides decreased more significantly with acarbose treatment (P = 0.03) ConclusionsSignificantly higher rates of treatment-adherence and at-target glycemic levels were seen with repaglinide treatment. Weight decreased with acarbose and increased with repaglinide treatment. Hypoglycemic episodes were much less frequent with acarbose treatment.

Herbal Formula Gegen-Qinlian Decoction for Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Background Herbal formula Gegen-Qinlian Decoction (GQD) has been widely used in China for the treatment of type 2 diabetes mellitus (T2DM), but its efficacy and safety are unclear. Method The studies were identified from the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure database, Wanfang database, and VIP database using the keywords “Gegenqinlian” or “Gegen-Qinlian” or “Gegen-Qin-Lian” or “Ge Gen Qin Lian.” Relevant studies were selected according to predefined inclusion and exclusion criteria. Study selection, data extraction, and validation were carried out by, at least, two reviewers with disagreements being settled by discussion. Results After literature search, a total of 26 randomized controlled trials were included with a total of 2553 patients. There was evidence that compared with metformin, the combination of GQD and metformin significantly reduced the fasting plasma glucose levels (MD −1.79, 95% CI (−2.31, −1.27), p < 0.00001); 2-hour postprandial plasma glucose levels (MD −1.72, 95% CI (−2.12, −1.31), p < 0.00001); and glycosylated hemoglobin levels (MD −1.26, 95% CI (−1.80, −0.72), p < 0.00001), and no serious side effects were identified. Conclusion These data suggest that GQD may be an effective herbal formula in treating T2DM without serious side effects. The addition of GQD also enhances the hypoglycemic effects of metformin. However, the evidence remains weak due to methodological flaws, which may amplify the therapeutic benefit of GQD.

Low-intensity inspiratory loaded exercises improve physical health perception in women with type 2 diabetes

IntroductionPhysical exercises improve quality of life in type 2 diabetes. Inspiratory muscle exercises may be an alternative option for diabetic patients with physical disabilities unable to engage in physical exercises. The purpose of this study was to investigate the effect of inspiratory muscle exercises on physical and mental health dimensions of the 12-Item Short Form (SF-12) Health Survey in women with type 2 diabetes.MethodsOverall, 26 women with type 2 diabetes were allocated to the control (&lt;i&gt;n&lt;/i&gt; = 14) or study group (&lt;i&gt;n&lt;/i&gt; = 12). They were obese, aged 30–55 years, receiving oral hypoglycaemic medications. The inspiratory loaded exercise target intensity was 30% of maximal inspiratory pressure; sessions lasting 15–25 min were held on 5 days per week for 8 weeks. Quality of life was assessed as a primary outcome with the SF-12 questionnaire. Fasting and 2-hour postprandial blood glucose levels were measured as secondary outcomes.ResultsCompared with the control group, significant improvements were observed in the study group after the intervention in all SF-12 physical health domains and in SF-12 role emotional and social functioning mental health domains. In addition, fasting blood glucose was reduced from 134 ± 40 to 126.8 ± 51 mg/dl, which was a non-statistically but clinically significant change.ConclusionsLow-intensity inspiratory loaded exercises could be viewed as a successful alternative to physical exercises in improving physical quality of life in type 2 diabetic women. Health professionals interested in exercise therapy for type 2 diabetes may consider our findings.

Evaluation of Fasting Capillary Glucose and Fasting Plasma Glucose as Screening Tests for Diabetes and Prediabetes among Adults in a Semi-Urban Area in the Kathmandu District, Nepal

The natural history of type 2 diabetes includes a preceding period of impaired fasting glucose or impaired glucose tolerance which is referred to as prediabetes. During the asymptomatic phase of prediabetes, an estimated 20-30% of persons may develop complications like retinopathy, cardiovascular disease, neuropathy and nephropathy. Screening and lifestyle management may help to delay or arrest progression to diabetes. In primary care settings, point of care devices that measure glucose in capillary blood can be used for diagnosis of diabetes. This study was carried out to evaluate the performance of fasting capillary glucose (FCG) and fasting plasma glucose (FPG) measurement in screening for diabetes and prediabetes among adults in a semi-urban community in the Kathmandu district of Nepal. An observational, cross-sectional study design was used and FCG, FPG performance was evaluated by the 2-hour plasma glucose levels (2-hr PG) following Oral glucose tolerance test (75g glucose) using WHO 1998 criteria. Linear regression was performed to assess correlation co-efficient (r) between FPG, FCG and 2 hr PG. Bland Altman plot and Receiver operator characteristic (ROC) curves were constructed to assess concordance, measure ROC AUC and determine sensitivity and specificity of the measurements at recommended cut-off values for identifying diabetes and prediabetes. Among the study participants (n=162), 104 were female and 58 were male. Prevalence of undiagnosed diabetes and prediabetes was 4.32% (95% CI 1.75% to 8.70%) and 7.14% (95% CI 3.89% to 12.58%). Strong positive correlation was seen between FPG and FCG (Spearman’s r 0.67). FPG &amp; FCG had a moderate positive correlation (r = 0.49 &amp; 0.45) with 2 hr PG levels (p&lt;0.0001). FCG and FPG ROC AUC was 0.91 (95% CI 0.85 to 0.97) and 0.87 (95% CI 0.78 to 0.97) in comparison to 0.98 (95% CI 0.97 to 1.0) for the gold standard 2 hr PG. At 110 mg/dl and above, FCG had an optimal sensitivity and specificity of 84.21% and 81.12% in comparison to 47.37% and 100% for FPG. At 100 mg/dl, the sensitivity and specificity of FCG was 100% and 51.75% in comparison to 57.89% and 97.20% for FPG. In conclusion, at each recommended cut-off value, FCG was more sensitive than FPG with no significant difference between ROC AUCs of the two tests. Hence, FCG may be a suitable, sensitive, and convenient screening tool for diabetes and prediabetes in community-based settings. Larger prospective studies may validate the cost-effectiveness and efficiency of similar screening strategies in the Nepalese community.

Impaired glucose tolerance among adolescents with low birth weight history: The Tanjungsari Cohort Study in Indonesia.

Diabetes prevalence has been increasing overtime in Indonesia along with its complications and morbidities. Diabetes prevention program is still a challenge. Previous study concluded poor intrauterine nutritional status, low birth weight (LBW), and nutrition status early in life were risk factors for impaired glucose tolerance (IGT) or type 2 diabetes mellitus in adulthood. This study aimed to evaluate the association between both LBW and intrauterine growth restriction (IUGR) with IGT in adolescents. Total of 536 subjects from Tanjungsari Cohort Study were included in this study. Subjects were in their early adolescence age (12-14 years). Anthropometric data were collected and IGT was determined by using 2- hour postprandial plasma glucose level, then it was assessed based on their birth weight and intrauterine nutritional status. Subjects with LBW history were shorter, had lower body weight and body mass index (p<0.05, respectively). The proportion of IGT is significantly higher among subject with LBW (RR 1.692 [1.079- 2.653]). There was no difference on proportion of IGT among subjects with IUGR compared with subjects who were not IUGR or born preterm (p=0.286). Multiple regression analysis showed the effect of LBW remain independent after adjusted with sex and socioeconomic variables (RR 1.650 [1.054-2.584]). Significant association was found between LBW and IGT in comparison to those who were born with normal birth weight. Hence, diabetes should be prevented as early as possible, even since in the pregnancy.

Efficacy of Chinese Herbal Medicine in the Treatment of Moderate-Severe Painful Diabetic Peripheral Neuropathy: A Retrospective Study.

Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of diabetes. The aim of this retrospective study was to investigate the effectiveness of a Chinese herbal medicine regimen—the modified Huangqi Guizhi Wuwu Decoction (HGWD)—in the treatment of moderate-severe pDPN. The primary objective was to estimate the improvement in neuropathic pain severity. The secondary objective was to assess the response of common symptoms to the treatment. The change in patients' blood glucose level during the whole treatment was also evaluated. By searching through our medical records of all the diabetic patients from January 2006 to January 2012, we identified and enrolled 30 moderate and severe pDPN patients in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed. The modified HGWD treatment was administered orally twice a day for 6 months. The numerical rating scale (NRS) level at month 6 was 2.57 ± 2.30, significantly improved compared with the baseline level of 6.03 ± 1.83 (P < 0.05). The amelioration of 3 common symptoms, namely, limb pain, limb numbness, and insomnia, was evident, and the major response of common symptoms at month 6 including limb pain, insomnia, and limb coldness was significantly increased compared with the results at month 3 (P < 0.05). Moreover, 2-hour postprandial blood glucose (2hPG) level decreased from 10.77 ± 1.29 mmol/L at baseline to 9.66 ± 0.60 mmol/L at month 6 (P < 0.05). No serious adverse events occurred throughout the treatment period. The modified HGWD was effective in the treatment of moderate and severe pDPN and can thus be offered as a new alternative treatment option for pDPN patients who failed to respond to regular pharmaceutical therapies.

Effect of the Pregnant+ smartphone application in women with gestational diabetes mellitus: a randomised controlled trial in Norway

ObjectiveTo assess the effect of the Pregnant+ app on the 2-hour glucose level of the routine postpartum oral glucose tolerance test (OGTT) among women with gestational diabetes mellitus (GDM). The...

Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China.

BackgroundDiabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes.Methods and findingsWe conducted a population-based retrospective cohort study among 6,447,339 women aged 20–49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6–6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06–1.09; P < 0.001), PTB (1.02; 1.01–1.03; P < 0.001), macrosomia (1.07; 1.06–1.08; P < 0.001), SGA (1.06; 1.02–1.10; P = 0.007), and perinatal infant death (1.08; 1.03–1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07–1.15; P < 0.001), 1.17 (1.14–1.20; P < 0.001), 1.13 (1.09–1.16; P < 0.001), 1.17 (1.04–1.32; P = 0.008), and 1.59 (1.44–1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15–1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend <0.001, <0.001, <0.001, 0.001, <0.001). Information about hypoglycemic medication before or during pregnancy was not collected, and we cannot adjust it in the analysis, which could result in underestimation of risks. Data on 2-hour plasma glucose level and HbA1c concentration were not available, and the glycemic control status was evaluated according to FPG value in women with DM.ConclusionsWomen with preconception IFG or DM had higher risk of adverse pregnancy outcomes, including spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death. Preconception glycemic control through appropriate methods is one of the most important aspects of preconception care and should not be ignored by policy makers.

Plasma Metabolomics to Identify and Stratify Patients With Impaired Glucose Tolerance.

Impaired glucose tolerance (IGT) is one of the presymptomatic states of type 2 diabetes mellitus and requires an oral glucose tolerance test (OGTT) for diagnosis. Our aims were twofold: (i) characterize signatures of small molecules predicting the OGTT response and (ii) identify metabolic subgroups of participants with IGT. Plasma samples from 827 participants of the Study of Health in Pomerania free of diabetes were measured using mass spectrometry and proton-nuclear magnetic resonance spectroscopy. Linear regression analyses were used to screen for metabolites significantly associated with the OGTT response after 2 hours, adjusting for baseline glucose and insulin levels as well as important confounders. A signature predictive for IGT was established using regularized logistic regression. All cases with IGT (N = 159) were selected and subjected to unsupervised clustering using a k-means approach. In total, 99 metabolites and 22 lipoprotein measures were significantly associated with either 2-hour glucose or 2-hour insulin levels. Those comprised variations in baseline concentrations of branched-chain amino ketoacids, acylcarnitines, lysophospholipids, or phosphatidylcholines, largely confirming previous studies. By the use of these metabolites, subjects with IGT segregated into two distinct groups. Our IGT prediction model combining both clinical and metabolomics traits achieved an area under the curve of 0.84, slightly improving the prediction based on established clinical measures. The present metabolomics approach revealed molecular signatures associated directly to the response of the OGTT and to IGT in line with previous studies. However, clustering of subjects with IGT revealed distinct metabolic signatures of otherwise similar individuals, pointing toward the possibility of metabolomics for patient stratification.

Hyperglycemia and Adverse Pregnancy Outcomes.

For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.

Effect of antituberculosis treatment on dynamics of carbohydrate and lipid profile

Objective — study the effect of antituberculosis treatment on the dynamics of carbohydrate and lipid profile in patients with newly diagnosed pulmonary tuberculosisMaterials and methods. We examined 76 patients with drug-susceptible pulmonary tuberculosis and 64 patients with drug-resistant pulmonary tuberculosis. The treatment was carried out according to the current order of the Ministry of Health of Ukraine. Material for the study (venous blood) was collected before treatment and one month later in the morning on an empty stomach. Additionally, an oral glucose tolerance test was performed, the fasting insulin level was determined, the lipid profile was measured, the insulin resistance index (HOMA-IR) and atherogenic index of plasma were calculated. For statistical processing used the software package Statistica for Windows version 13.2.Results and discussion. In the process of treatment with І-line antituberculosis drugs, the level of glucose in 2 hour GTT increased from 4.34 mmol/L to 5. 29 mmol/L. In patients who received ІI-line antituberculosis drugs, the glucose level decreased from 5.77 mmol/L to 4.33 mmol/L, and the fasting insulin level also decreased from 16.30 to 14.47 µcU/mL; the median level of insulin resistance decreased from 3.31 to 2.22 (p = 0.0057). In the process of treatment we found a significant decrease in VLDL levels (р = 0.0028) in drug-susceptible tuberculosis patients. Due to treatment, mean value of HDL-c in in drug-susceptible tuberculosis patients increased slightly from 1.01 mmol/L till 1.12 mmol/L, while in drug-resistant tuberculosis patients it decreased significantly (р=0.0171) from 1.07 mmol/L till 0.94 mmol/L.Conclusions. We found the negative effect of І-line antituberculosis drugs on the carbohydrate metabolism of patients with pulmonary tuberculosis, which manifested as impared glucose tolerance, which makes it possible to recommend OGTT for objectivizing the effect of anti-tuberculosis drugs on carbohydrate metabolism. While in patients who were treated with IІ-line antituberculosis drugs, we found a significant decrease in 2-hour glucose level and fasting insulin level, which indicates the modeling effect of these drugs on carbohydrate metabolism. Our findings suggest that drug-susceptible tuberculosis treatment had a positive effect on the lipid metabolism, which was manifested by the growth of the anti-atherogenic pool of lipoproteins and the decrease in very low-density lipoprotein level. At the same time, we found a negative effect of drug-resistant tuberculosis treatment on lipid metabolism, which manifested as increase of atherogenic index of plasma due to increase of total cholesterol level in patients with newly diagnosed pulmonary tuberculosis.

1531-P: Spontaneous Ketonuria Is Associated with Reduced Incidence of Diabetes

Objective: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance still remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic parameters in a large population-based, observational study. Research Design and Methods: We analyzed a total of 8,703 individuals free of diabetes at baseline in the Korean Genome and Epidemiology Study, a community-based, 12-year prospective study. Subjects with (n=195) or without fasting ketonuria were 1:4 matched by propensity score. Incident diabetes was defined as: fasting plasma glucose ≥126 mg/dL, 2-hour glucose ≥200 mg/dL on biennial 75g oral glucose tolerance test, or current antidiabetic medication. Using Cox regression models, hazard ratios for developing diabetes associated with the presence of ketonuria at baseline were analyzed. Results: Over 12 years, of the 925 subjects in the propensity score matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in subjects with spontaneous ketonuria compared to those without ketonuria (adjusted hazard ratio 0.64 [95% confidence interval=0.42-0.99]. This result was replicated in the whole cohort (HR 0.67 [95% CI: 0.46-0.98] after multivariate adjustment). During follow-up, subjects with ketonuria at baseline maintained lower 1-hour and 2-hour glucose levels, and a higher insulinogenic index during follow-up despite comparable baseline values. Conclusions: The presence of spontaneous fasting ketonuria was significantly associated with a reduced incidence rate of diabetes, independently of metabolic parameters. Our findings suggest spontaneous fasting ketonuria is a stable phenotype and a novel signature in the modulation of glucose metabolism. Disclosure S.J. Cho: None. I. Lee: None. S. Lee: None. E. Kang: None. E. Ferrannini: None. Y. Lee: None. G. Kim: None. B. Cha: None.

1612-P: Insulinogenic Index and HOMA-ß Are Independent Risk Factors for Future Type 2 Diabetes

β-cell dysfunction is major risk factor for type 2 diabetes. As HOMA-β reflects fasting β-cell function and insulinogenic index reflects early phase insulin response during an oral glucose tolerance test (OGTT), these two indices represent different aspects of insulin and glucose metabolism. It is not known whether HOMA-β and insulinogenic index are independently associated with type 2 diabetes risk. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. Insulin sensitivity was assessed by HOMA-IR. β-cell activity was assessed by HOMA-β [fasting plasma insulin (μU/mL) × 360/(fasting plasma glucose (mg/dL) - 63)] and the insulinogenic index [Δinsulin (30-0 min) (μU/mL)/Δglucose (30-0 min) (mg/dL)] obtained during a 75-g OGTT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. Logistic regression analysis was used to estimate odds ratios (OR) of incident diabetes. A total of 95 participants developed type 2 diabetes over 10-11 years. Insulinogenic index and HOMA-β were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included insulinogenic index, HOMA-β, HOMA-IR, age, BMI, gender, and family history of diabetes, OR of future type 2 diabetes for tertile 2 and 3 of insulinogenic index were 0.43 (95% CI, 0.22-0.85) and 0.31 (0.14-0.67), respectively, compared to tertile 1, and those for tertile 2 and 3 of HOMA-β were 0.31 (0.14-0.69) and 0.25 (0.10-0.63), respectively, compared to tertile 1. HOMA-IR was also associated with the risk of type 2 diabetes independent of these two indices. OR of tertile 2 and 3 of HOMA-IR were 1.75 (0.82-3.74) and 9.17 (3.78-22.28), respectively, compared to tertile 1. In conclusion, both higher insulinogenic index and HOMA-β were independently associated with a lower risk of type 2 diabetes independent of insulin sensitivity. Disclosure K.K. Sato: None. T. Hayashi: None. S. Uehara: None. Y. Onishi: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None.

226-LB: HOMA-ß and ß-Cell Activity in Early and Late Phase during an OGTT Are Independent Risk Factors of Type 2 Diabetes in Japanese Americans

The β-cell plays a major role in type 2 diabetes (T2DM). HOMA-β reflects fasting β-cell activity. Insulin responses during an OGTT reflect β-cell activity during glucose loading, which has two phases, early and late. HOMA-β, early, and late β-cell activity have different pathophysiologies. However, no research has examined whether HOMA-β and early and late phase β-cell activity during an OGTT are independently associated with the risk of T2DM. In a prospective cohort study, 415 nondiabetic Japanese-American men and women were followed for 10-11 years. β-cell activity was assessed by HOMA-β [fasting insulin × 360/(fasting glucose − 63)] as fasting activity, the insulinogenic index (IGI) [?insulin (30-0 min)/?glucose (30-0 min)] during an OGTT as early phase activity, and (area under the curve (AUC) of insulin 60-120 min)/(AUC glucose 60-120 min) as late phase activity. Insulin sensitivity was estimated by Matsuda index [10000/square root of ((fasting glucose) × (fasting insulin) × (AUC glucose 0-120 min/120) × (AUC insulin 0-120 min/120))]. T2DM was diagnosed as fasting plasma glucose level ≥126 mg/dL, 2-hour glucose level ≥200 mg/dL, or taking glucose-lowering medications. During the 10-11 year follow-up, 95 cases of T2DM occurred. HOMA-β, IGI, and late phase β-cell activity were all independently associated with the risk of T2DM. Multiple-adjusted odds ratios of T2DM for tertile 1, 2, and 3 of HOMA-β were 1.00 (reference), 0.25 (95% CI, 0.11-0.57), and 0.14 (0.05-0.37), respectively; those of IGI were 1.00, 0.35 (0.17-0.75), and 0.19 (0.07-0.47), respectively; and those of late phase β-cell activity were 1.00, 0.34 (0.14-0.82), and 0.16 (0.05-0.53), respectively, in the model that included HOMA-β, IGI, late phase β-cell activity, Matsuda index, age, BMI, sex, and family history of T2DM. In conclusion, higher β-cell activity while fasting and in both the early and late phase during an OGTT were all independently associated with a lower risk of T2DM. Disclosure T. Shimojo: None. C. Izumi: None. K.K. Sato: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None.

1666-P: Metabolic Characteristic of Elevated One-Hour Plasma Glucose Levels during a 75g Oral Glucose Tolerance Test in the Nonobese Japanese Men

It has been shown that subjects with normal glucose tolerance (NGT) but elevated 1-hour glucose level ≧155 mg/dl during a 75g oral glucose tolerance test (75g OGTT) is an independent risk factor for type 2 diabetes. In Caucasian, subjects with elevated 1-h glucose were characterized by adiposity with lower insulin sensitivity and impaired beta-cell function. While type 2 diabetes in Asians is frequently affected in non-obese (BMI&amp;lt;25 kg/m2) subjects, the characteristics of non-obese Asians with elevated 1-h glucose are totally unknown. Here, we studied 59 non-obese Japanese men with NGT. Based on the level of 1-hour glucose level during 75g OGTT, we divided the subjects into Low-1 hour group (&amp;lt; 155mg/dl) and High-1 hour group (≧155mg/dl). We measured ectopic fat in muscle and liver and subcutaneous and viscera fat areas by 1H-MRS and MRI, respectively. We also measured tissue specific insulin sensitivity by 2 step hyperinsulinemic-euglycemic clamp. Insulinogenic index (0.66±0.30 vs. 1.41±1.21ΔInsulin0-30 min/ΔGlucose 0-30min, p=0.02) was significantly lower and area under the curve of glucose and insulin during 75g OGTT were significantly higher in High-1 hour group than Low-1 hour group (Figure). However, other parameters including insulin sensitivity and ectopic fat in muscle and liver, subcutaneous and viscera fat areas were comparable between the groups. These data suggest that non-obese Japanese men with High-1 hour glucose are characterized by impaired early-phase insulin secretion and subsequent hyperinsulinemia. Insulin resistance and abnormal fat distribution are not evident in this population. Disclosure M. Sato: None. Y. Tamura: None. H. Kaga: None. Y. Someya: None. S. Kakehi: None. N. Yamasaki: None. D. Sugimoto: None. S. Kadowaki: None. R. Suzuki: None. Y. Furukawa: None. K. Takeno: None. T. Funayama: None. R. Kawamori: None. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

73-LB: Improvements in Sleep Quality after Cognitive Behavioral Therapy for Insomnia Are Associated with Improved 2-Hour Post-Load Glucose

Poor-quality sleep may be a possible modifiable risk factor in the development of T2DM. We conducted a pilot clinical trial (N=17) to examine the effects of insomnia treatment on insulin resistance in persons with prediabetes. Participants received up to 7 sessions of cognitive behavioral therapy for insomnia (CBT-I), a highly effective, first-line treatment for insomnia. Before and after CBT-I, participants underwent 75-gram oral glucose load test and wore wrist Actiwatches (ActiGraph GT9X Link) to measure sleep indices. Actigraphy data were collected, including wake after sleep onset (WASO; length of periods of wakefulness after sleep onset) and sleep efficiency (SE; ratio of time asleep to time in bed). We calculated the correlation between change in 2-hour post-load glucose and change in WASO and SE in those who completed treatment (at least 6 sessions of CBT-I; N=13). Decreases in WASO and increases in SE after CBT-I (indicating improved sleep) were associated with decreased 2-hour post load glucose levels (see Figure). The estimated Pearson correlations indicated medium-large effect sizes per Cohen’s rule, suggesting a potential reduction in the risk of full T2DM. This small pilot study shows the need for further research on whether treatment of insomnia improves glucose tolerance. Disclosure E.S. LeBlanc: None. N. Smith: None. M. Allison: None. G. Clarke: None. Funding Kaiser Permanente

1684-P: Using Index60 to Detect Heterogeneity and Identify Subpopulations with Characteristic Type 1 Diabetes (T1D) Profiles among Individuals with Normal Two-Hour Glucose Levels

We assessed whether Index60 could identify subpopulations with heterogeneous T1D features among autoantibody positive (Ab+) individuals with a normal 2-hour glucose. Index60 is a composite measure of fasting C-peptide, 60-minute C-peptide, and 60-minute glucose that has potential utility as a prediabetes endpoint when values are ≥1.00. Baseline 2-hour OGTTs of Ab+ TrialNet Pathway to Prevention participants in the normal 2-hour glucose (&amp;lt;140 mg/dl) range and low Index60 range (&amp;lt;1.00) were studied. The top 2-hour glucose &amp;lt;140 mg/dl quartile was compared with the top Index60 &amp;lt;1.00 quartile for characteristic T1D features (groups mutually exclusive). Those in the top Index60 quartile (Group B) or in both top quartiles (Group C) had profiles more typical of T1D than those in the top 2-hour glucose quartile (Group A), who had higher C-peptide levels, lower Ab+ frequencies, and were older (Table). Also, as indicated by within group odds ratios, Group A had less association of DR3-DQ2/DR4-DQ8 with the top quartile (Group A: 1.19, ns; Group B: 1.49, p&amp;lt;0.01; Group C: 1.63, p&amp;lt;0.01). In summary, Index60 can detect heterogeneity among those with normal 2-hour glucose levels, and identify subpopulations with appreciably more characteristic T1D features. The atypia of Group A demonstrates the importance of this Index60 utility. Disclosure B.M. Nathan: None. S. Geyer: None. L.E. Bocchino: None. J.P. Palmer: None. L.M. Jacobsen: None. M.J. Redondo: None. E.K. Sims: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. J.M. Sosenko: None. Funding National Institutes of Health; JDRF

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans.

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

OR31-5 Characterization of the One-Hour Plasma Glucose and Plasma Insulin during an Oral Glucose Tolerance Test (OGTT) in Obese Hispanic Children and Adolescents Diagnosed with Prediabetes (Hba1c ≥ 5.7% &amp; ≤ 6.4%)

Background: OGTT is still considered the gold standard test to detect prediabetes and /or Type 2 diabetes (T2D). American Diabetes Association criteria for prediabetes: a) Hba1c 5.7- 6.4% b) fasting plasma glucose (FPG) ≥ 100 mg/dl and/or post-prandial PG ≥ 140, Impaired glucose tolerance (IGT) during an OGTT. In adults the 1-hour(1hr) glucose level (≥ 155 mg/dl) is a strong predictor of future T2D risk than the two-hour level and is associated with diabetes complication. The ideal cut-off for pediatrics is not established though studies have found 1hPG ≥ 132.5 mg/dl, as predictive for risk of T2D (1) Objective: a. To study the dynamic profile of Plasma Glucose (PG) and plasma Insulin (PI) values at time 0,1 and 2 hour during an OGTT b. to assess whether degree of insulin resistance in Hispanic children and adolescents can be predict an abnormal I hr glucose level. Methods: We reviewed OGTT results of 43 obese Hispanic youths; 7-18 years of age with prediabetes. PG and PI values were obtained at 0, 1 and 2hr during OGTT (glucola: dose of 1.75 g/kg body weight up to a maximum of 75 g). The Homeostasis Model Assessment of fasting insulin resistance (HOMA-IR), an index of insulin resistance was calculated using (fasting glucose (mg/dl) X fasting insulin(µIU/ml)/405) and values ≥3.4 were taken as insulin resistance(2). Independent T test was used to study differences between means for group1: HOMA-IR< 3.4 and group 2: HOMA-IR≥ 3.4. Results: Forty-three obese Hispanic youths; 7-18 years of age; mean age of 11.5 ± 0.7; BMI=42.2 ± 4.9; 47% male and 53% female. a) OGTT results: Only one subject had abnormal fasting plasma glucose, 3 subjects had IGT (7%), and 11(26%) had an abnormal 1 h PG during the OGTT b) 1hr glucose and 1hr insulin was different between HOMA-IR groups (p=0.001) even though 2-hr was not. PG: grp#1: 1hr=108 ± 27, 2hr=107 ± 33 mg/dl; grp #2: 1hr=136 ± 33, 2hr=120 ± 32. PI: grp#1: 1hr= 80 ± 61, 2hr= 78 ± 70; grp#2: 1hr= 213 ±171, 2hr= 99 ± 375. Conclusion: In our Hispanic children and adolescents, 1& 2-hr plasma insulin and plasma glucose were clearly abnormal, more so, in the HOMA- IR group ≥ 3.4. This demonstrate that at least in the IR children and adolescents, 1-hour values add value to the interpretation of the OGTT. 26 % of Hispanic children and adolescents had an abnormal 1-hr glucose which is a novel finding of our study. These results validate the recent reports of the plasma 1-hr glucose threshold ≥132.5 mg/dl in Pediatrics and prospective follow up of these Hispanic patients will be able to demonstrate the predictive value of 1 hr values of insulin and glucose to development of T2D.Reference: ADDIN EN.REFLIST 1. Manco M, Miraglia Del Giudice E, et al. 1-Hour plasma glucose in obese youth. Acta diabetologica. 2012;49(6):435-43. 2. Brar PC, Screening obese children and adolescents for prediabetes and/or type 2 diabetes in pediatric practices: a validation study. Clinical pediatrics. 2014;53(8):771-6.

Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Randomized Controlled Trial.

Impaired awareness of hypoglycemia (IAH), resulting from habituation to recurrent hypoglycemia, can be reversed by strict avoidance of hypoglycemia. Adjunctive treatment with glucagon-like peptide-1 receptor agonists may reduce glucose variability, hence lower the risk of hypoglycemia and improve awareness. The aim of our study was to investigate the effect of exenatide on awareness of hypoglycemia in patients with type 1 diabetes and IAH. This was a randomized double-blind, placebo-controlled crossover trial. Ten patients with type 1 diabetes and IAH were included [age, 38.5 ± 4.4 years; 40% males; glycated hemoglobin 7.2% ± 0.4% (55.2 ± 4.8 mmol/mol)]. Patients were treated with exenatide 5 µg twice daily (first two weeks), followed by 10 µg twice daily (remaining four weeks) or matching placebo, with a four-week washout period. Patients wore blinded glucose sensors in the final weeks and modified hyperinsulinemic normoglycemic-hypoglycemic glucose clamps (nadir 2.5 mmol/L) were performed at the end of each treatment period. Treatment with exenatide caused body weight to decrease compared with placebo (-3.9 ± 0.9 vs 0.6 ± 1.2 kg, P = 0.047). Exenatide did not change mean 24-hour glucose levels (8.3 ± 0.4 vs 8.5 ± 0.3 mmol/L, exenatide vs placebo, P = 0.64), median (interquartile range) percentage of time spent in hypoglycemia [15.5 (4.5, 25.5) vs 7.8 (4.4, 17.1)%, P = 0.11] and frequency of hypoglycemia (15.8 ± 3.7 vs 12.1 ± 3.5, P = 0.19). Symptom scores in response to clamped hypoglycemia were similar between exenatide [median change 1.0 (-1.5, 7.0)] and placebo [4.5 (1.5, 5.8), P = 0.08]. Six weeks of treatment with exenatide did not improve awareness of hypoglycemia in patients with type 1 diabetes and IAH.