Postload Blood Glucose Levels Research Articles

1465-P: Identification of GCK Gene Variants and Clinical Characterization in Japanese Pediatric MODY2 Cases

Maturity-onset diabetes of the young (MODY) is traditionally characterized by early onset and a heterogeneous autosomal dominant form of inheritance. MODY2 may be common in the Japanese, but the difference in clinical characteristics compared to Europeans and Americans remains unclear. Here, we examined the characteristics in Japanese pediatric patients diagnosed with MODY2. We retrospectively reviewed the diagnostic data of Japanese MODY2 patients diagnosed at our hospital between 2009 and 2022. Genetic screening for MODY2 was performed by direct sequencing followed by multiplex ligation amplification assays. We identified 20 missense mutations in 25 patients and 2 nonsense mutations in 2 patients. We detected 5 deletions in 6 patients. The mean age at diagnosis was 10 years (range 2-14 years), the mean BMI percentile was 46.2%, with none being obese. Mean HbA1c was 6.54%. A glucose tolerance test was performed on 29 patients, 15 of whom were diabetic (7 were diabetic at fasting, 5 were diabetic at 120 min, 3 were diabetic at both) and 14 of borderline diabetes (IFG + IGT: 11, IFG: 2, and IGT: 1). The average glucose tolerance test values were 121.6 mg/dL at 0 min and 182.2 mg/dL at 120 min. No correlation was found between age at onset and plasma glucose value at 0 and 120 min. Reportedly, MODY2 causes a slight increase in post-load blood glucose levels, however the difference between 120 min and 0 min was 56.0 mg/dL (−32 to 140). A negative correlation was observed between 0 min and 120 min blood glucose levels. HOMAIR average was 1.85, 27% of which patients were 2.5 or higher; HOMA-β average was 37.0%, 39% of which showed <30%; and insulinogenic index averaged 0.63, 25% of which showed <0.4, indicating decreased initial insulin secretion. In this study, it is suggested that in Japanese MODY2 cases, glucose sensor dysfunction due to GCK gene mutation causes decreased initial insulin secretion. Disclosure R.Katashima: None. S.Yoshida: None. Y.Watanabe: None. M.Moritani: None. I.Yokota: None.

Comparative effectiveness of acupuncture and pharmacological interventions in treating diabetic stroke: A protocol for a systematic review and network meta-analysis.

There is a close and causative correlation between stroke and diabetes, and the complication of the 2 diseases seriously harms human health and currently becomes a topic of clinical importance. To date, the common methods of treating diabetic stroke include acupuncture and pharmacological interventions. However, there is no high-quality or direct evidence of their comparative effectiveness. This review aims to provide a network meta-analysis to compare the efficacy of acupuncture and pharmacological interventions in treating diabetic stroke. Databases such as PubMed, Cochrane Central Register of Controlled Trials, EMBASE, China National Knowledge Infrastructure, China Biology Medicine Disc will be searched for relevant randomized controlled trials to obtain literatures on the treatment of diabetic stroke, and clinical randomized controlled trials will be screened out from their inception to December 30, 2022. The participant intervention comparator outcomes of this study are as flowing: P, patients with diabetic stroke; I, acupuncture and pharmacological interventions; C, no treatment, pharmacological placebo, or sham acupuncture groups; O, primary outcome will be blood glucose levels, glycosylated hemoglobin levels, and the rate of stroke recurrence; secondary outcomes will include fasting and post-load blood glucose levels, cholesterol, triglycerides, and quality of life scale scores. Cochrane Risk of Bias Tool will be used in assessing literature's quality. Review Manager software 5.3 and Stata 15.1 will be used in data analysis. This systematic review and network meta-analysis will provide evidence of the efficacy of different therapeutic methods in treating diabetic stroke, to show which forms of therapy are more commonly used with higher effectiveness. The results will systematically provide suggestions for medical practitioners to choose the effective, time-saving and economical therapeutic strategy for diabetic stroke.

Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats

BackgroundTreatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats.MethodsMale ZDF rats and Zucker lean rats aged 4–8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed.ResultsData demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats.ConclusionsThese results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.

1436-P: Gestational Diabetes Pregnancy by Pregnancy

Gestational diabetes mellitus (GDM) is a risk factor for GDM in next pregnancies.The aims of this observational study are to measure GDM recurrence rate in post index pregnancy of women with prior GDM and to compare maternal and neonatal outcomes and pancreatic beta cells function in two consecutive pregnancies. Methods: Longitudinal observational study in 68 women with GDM in index pregnancy (G1), followed by a post index pregnancy (G2) and normal glucose tolerance in-between [G1 vs. G2: age 32,1±4,6 vs. 35,5±4,7 years, BMI 24,5 (19,2-42,7) vs. 24,7 (17,5-42,2) kg/m2, ns]. GDM diagnosis according to IADPSG criteria. Statistics: SPSS. Results: significantly earlier first visit gestational age in G2 [17 (6-36) weeks] than in G1 [28,5 (8-35) weeks] (p<0,001). GDM recurrence rate was 85,3% (n58) 3,32±1,8 years after index pregnancy: of these women, n31 (45,6%) [36.5±4 years; BMI 24.7 (19.3-42.1) Kg/m2] developed GDM in early pregnancy (16-18 weeks), while n27 (39,7%) [35.66±4 years; BMI 25.26 (17.6-42.2) Kg/m2] at the end of second trimester (24-28 weeks). Women who reported a negative OGTT at both time-points (n10, 14,7%) [33.7±5.5 years; BMI 20.45 (17.5-25.4) Kg/m2;] showed a significantly lower BMI (p<0,0015) and a higher disposition index (p=0.07) than those with positive OGTT. In women who did not relapse GDM, no significant inter-pregnancy weight gain was observed and GDM diagnosis in G1 was performed by post-load OGTT points. Lower 24-28thOGTT post load blood glucose levels and AUCglucose were found in G2 (p<0,02, Wilcoxon). No pancreatic beta cells function deterioration was recorded in post index pregnancy. We found a lower rate of cumulative neonatal adverse outcomes in G2 (30,2% in G1 vs. 25,7% in G2, p<0,04) and a reduced maternal hypertension rate even though it did not reach the level of significance (4vs8). Conclusions: GDM relapsed in the majority of women with previous GDM with no weight gain between pregnancies and no pancreatic function deterioration. However, a normal OGTT in second pregnancy was found in normoweight women. Disclosure C. Giuliani: None. O. Bitterman: None. F. Amorosi: None. C. Festa: None. A. Napoli: None.

The relationship between glycated hemoglobin, postload blood glucose levels and non-hdl cholesterol among 75 gram oral glucose tolerance test applied women

The relationship between glycated hemoglobin, postload blood glucose levels and non-hdl cholesterol among 75 gram oral glucose tolerance test applied women

Effect of broth from meat of linseed-fed cattle on glucose-stimulated insulin release in healthy male volunteers.

Polyunsaturated fatty acid consumption has been shown to improve insulin sensitivity. We studied if administration of broth with beef meat enriched with polyunsaturated fatty acids influenced glucose-stimulated insulin release in healthy male volunteers. Broth was made either from cattles undergone dietary supplementation with lightly bruised whole linseed in addition to feeding ad libitum on grass silage (test meal) or from those fed grass silage alone (control meal). Oral glucose tolerance tests (OGTT) were performed in patients after a 6-day period of eating 300ml broth containing 100g meat once a day in addition to their otherwise normal mixed nourishment. During OGTT, blood samples were taken for blood glucose level and plasma insulin immunoreactivity before and 15, 30, 60, 90, 120, and 180min after the glucose load. Glucose-stimulated maximum increase in plasma insulin immunoreactivity was 42±6.6 and 81±7.4mU/ml (p<0.05) after the test and the control meals, respectively. However, both fasting and postload blood glucose levels were the same after either meal period. The results suggest an insulin-sensitizing effect of food produced from beef cattle maintained on linseed diet in healthy human volunteers.

Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats

Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In DCM, insulin resistance may alter cardiac substrate supply and utilisation leading to changes in myocardial metabolism and cardiac function. In rats, exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may result in myocardial insulin resistance and cardiac functional changes resembling DCM. Rats received high-fat (HFD) or low-fat (LFD) diets for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile function and insulin signalling were assessed in papillary muscles and ventricular lysates, respectively. Fasting and post-load blood glucose levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed structural changes and triglyceride accumulation. HFD-muscles developed higher baseline and maximum forces, but showed impaired recovery from higher workloads. Insulin-associated modulation of Ca2+-induced force augmentation was abolished in HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol 3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of phospholamban, a critical regulator of myocardial contractility, was decreased in HFD-hearts (p < 0.05). HFD induced a hypertrophy-like cardiac phenotype, characterised by a higher basal contractile force, an impaired recovery from increased workloads and decreased insulin-mediated protection against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin resistance and phospholamban hypophosphorylation. Our data suggest that myocardial insulin resistance, resulting from exposure to excessive alimentary fat, may contribute to the pathogenesis of diabetes-related heart disease.

Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus

Objective: This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism. Study Design: This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations. Results: Oral glucose tolerance tests were done at a mean (±SD) of 24.9 ± 5.7 and 30.7 ± 3.2 weeks’ gestation, and amniotic fluid insulin measurements were done at 31.1 ± 3.2 weeks’ gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs 180 mg/dL; 9.3 vs 10.0 mmol/L; P =.0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 μU/mL; >42 pmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P =.002) during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test. Conclusion: Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal. (Am J Obstet Gynecol 2001;184:470-5.)

First degree family history of diabetes and risk factors for cardiovascular disease in non-diabetic subjects in the National Telephone Company: a metabolic survey.

The effect of first degree family history of diabetes on known risk factors for cardiovascular disease was evaluated in 4989 non-diabetic employees of the Italian Telephone Company. Family history of diabetes was present in 759 subjects (476 males and 283 females); in these subjects body mass index, diastolic blood pressure, blood glucose levels (fasting and one and two-hour post-load), triglyceride and cholesterol levels were significantly higher than in age and sex-matched controls. In different age groups (less than 30, 31-40, 41-50, greater than 50 years) the effect of first degree family history of diabetes was evaluated after stratification by sex. In males with first degree family history of diabetes, this effect was strongest in the under 30 age group: body mass indices, systolic and diastolic blood pressures, fasting and two-hour post-load blood glucose levels, triglyceride and cholesterol levels were all significantly higher than in subjects with negative family history of diabetes. These differences between subjects with negative and positive family histories declined with age and disappeared in subjects over 50. In females the effect of familial diabetes was weaker and delayed for body mass index and one hour blood glucose, appearing only in subjects over 30. Multiple logistic analysis indicated that only body mass index and one-hour blood glucose levels were independently associated with positive family history of diabetes. The differences observed between males and females in the youngest age group were also confirmed by this analysis. These data may indicate a multifactorial genetic link leading to increased cardiovascular morbidity in subjects with diabetes.

Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland.

The relationship of glucose tolerance to the incidence of coronary heart disease (CHD) has been investigated in two cohorts of Finnish men: 3267 men ages 40--59 yr from the Social Insurance Institution's (SII) Coronary Heart Disease Study and 1059 men ages 30--59 yr from the Helsinki Policemen Study. The relationship of plasma insulin level to the incidence of CHD was also investigated in the Helsinki Policemen Study. An oral glucose lead of 60, 75, or 90 g according to body surface area was used in both studies. In the SII Study, plasma glucose was determined from venous blood samples taken 1 h after glucose load. In the Helsinki Policemen Study, blood glucose was determined from venous blood samples taken at 0, 1, and 2 h, and at a 5-yr reexamination, plasma insulin was measured during OGTT at 0, 1, 2 h. In the SII Study cohort, the 4-yr mortality from CHD and the 4-yr incidence of nonfatal myocardial infarction (MI) did not show a definite relationship to 1-h postload plasma glucose. In the Helsinki Policemen Study cohort, the 5-yr incidence of "hard criteria" CHD (CHD death and nonfatal MI) was significantly related to high 1-h postload blood glucose level but not to fasting or 2-h postload blood glucose levels. 10-yr mortality from CHD was significantly higher in the top quintile of fasting and 1- and 2-h postload blood glucose levels, as was the incidence of "hard criteria" CHD. However, in multivariate analyses including age, systolic blood pressure, plasma cholesterol, and smoking, the blood glucose variables showed no statistically significant independent contribution in predicted risk of CHD. Univariate analyses by quintiles of plasma insulin levels measured at the 5-yr reexamination showed that the incidence of "hard criteria" CHD during the subsequent 5 yr was significantly higher in the top quintiles of fasting and 1-h and 2-h postload plasma insulin than in the combined lower quintiles. Multivariate analyses showed that the value of high 1-h or 2-h postload plasma insulin level for predicting CHD risk was independent of other risk factors, including blood glucose levels during OGTT.

Glucose tolerance and coronary heart disease: Helsinki Policemen Study

The relationship of glucose tolerance to the prevalence of symptoms and ECG signs of coronary heart disease (CHD), and to the 10-yr mortality from all causes, cardiovascular diseases and CHD was investigated in 867 Helsinki policemen aged 40–59 on whom an oral glucose tolerance test was carried out in 1966–1967. An oral glucose load of 75 or 90 g according to body surface area was used and blood glucose was determined fasting, 1 and 2 hr after the glucose load. Fasting and post-load blood glucose levels did not show any definite relationship to the prevalence of CHD symptoms (angina pectoris, history of verified myocardial infarction, non-verified severe chest pain attack) at the time of the initial examination, but these blood glucose variables showed a trend to a positive association to the prevalence of ischaemic ECG abnormalities. In multivariate analyses including age, systolic blood pressure, plasma cholesterol, body mass index and smoking, the blood glucose variables, however, failed to show a significant independent relationship to the prevalence of ECG abnormalities. In univariate analyses, a positive non-linear relationship was found between the blood glucose variables and the 10-yr mortality from all causes, cardiovascular diseases and CHD. The mortality rates were significantly higher in the top quintiles or deciles of 1-hr and 2-hr post-load blood glucose levels than in the corresponding combined lower quantiles. Fasting blood glucose showed similar trends, though these were not statistically significant. In multivariate analyses including age, systolic blood pressure, plasma cholesterol, body mass index and smoking, the blood glucose variables, however, did not show a significant independent contribution in the prediction of the 10-yr mortality from all causes, cardiovascular diseases or CHD.