Postprandial plasma glucose excursion is associated with an atherogenic lipid profile in individuals with type 2 diabetes mellitus: A cross-sectional study

Coronary heart disease (CHD) is a prevalent complication of type 2 diabetes mellitus (T2DM). The atherogenic low-density lipoprotein (LDL) cholesterol is an established risk factor of cardiovascular disease, and evidence also suggests that postprandial plasma glucose (PPG) levels closely delineate CHD mortality in diabetes. The investigators hypothesized that postprandial plasma glucose excursion (PPGE), defined as the difference between 2-hour PPG and fasting plasma glucose (FPG), may be associated with plasma LDL cholesterol levels in patients with T2DM. This study enrolled diabetic participants for whom FPG and lipid profile were sampled after a 12-hour fast, followed by PPG sampling two hours after consuming a standard meal with 75 grams of carbohydrates. The study enrolled 379 participants who were divided into PPGE tertiles according to the difference between their 2-hour PPG and FPG. Participants in the highest PPGE tertile had considerably greater plasma LDL cholesterol levels than patients in the lowest tertile (126.7 mg/dL vs. 99.5 mg/dL, P <0.001). Linear regression analysis also demonstrated that the PPGE was positively correlated with plasma LDL cholesterol levels (β coefficient: 0.165, P < 0.001). Postprandial glucose excursion positively correlated with plasma LDL cholesterol levels in individuals with T2DM. Participants with raised PPGE harbored greater LDL cholesterol levels than those with lower postprandial glucose fluctuations. Therefore, postprandial glucose excursion is associated with an atherogenic lipid profile and may be a modifiable risk factor of diabetic CHD.

Melanocortin 3 receptor-expressing neurons in the ventromedial hypothalamus promote glucose disposal

The ventromedial hypothalamus (VMH) is a critical neural node that senses blood glucose and promotes glucose utilization or mobilization during hypoglycemia. The VMH neurons that control these distinct physiologic processes are largely unknown. Here, we show that melanocortin 3 receptor (Mc3R)-expressing VMH neurons (VMHMC3R) sense glucose changes both directly and indirectly via altered excitatory input. We identify presynaptic nodes that potentially regulate VMHMC3R neuronal activity, including inputs from proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus. We find that VMHMC3R neuron activation blunts, and their silencing enhances glucose excursion following a glucose load. Overall, these findings demonstrate that VMHMC3R neurons are a glucose-responsive hypothalamic subpopulation that promotes glucose disposal upon activation; this highlights a potential site for targeting dysregulated glycemia.

Glycemic Variability Assessment with a 14-Day Continuous Glucose Monitoring System: When and How Long to Measure MAGE (Mean Amplitude of Glucose Excursion) for Optimal Reliability?

Mean amplitude of glucose excursion (MAGE) is considered as the “gold standard” for assessing the short-term within-day glycemic variability (GV), which is an important component of overall glycemic control. A 14-day continuous glucose monitoring system is now widely used and allows easier assessment of GV. However, it is still unknown whether MAGE, usually calculated on a 48-hour period is identical whatever the time during the 14-day lifespan of the sensor and whether a longer time period might give additional information. We evaluated in 68 patients with type 1 diabetes, MAGE during three 2-day periods (day1-day3; day6-day8; day11-day13) and during periods of 3 days and 4 days. MAGE calculated at the three 2-day periods were identical and not different from MAGE of the 3-day or 4-day periods.

Commercial Vinegar Tablets Do Not Display the Same Physiological Benefits for Managing Postprandial Glucose Concentrations as Liquid Vinegar

Objective. Research evidence suggests that vinegar may effectively reduce postprandial glucose in both healthy adults and those with type 2 diabetes. There is heightened consumer interest in commercially available vinegar tablets; however, it is not known whether these products lower postprandial glycemia to the same extent as liquid vinegar. This crossover trial examined the impact of liquid vinegar versus commercial vinegar tablet ingestion at the start of a meal on the 60-minute glucose excursion postmeal in healthy adults. Methods. Twelve young men and women (22.6 ± 0.6 y; 21.2 ± 1.2 kg/m2) completed this 4-arm Latin square crossover trial. Testing was separated by one week and consisted of a test meal (64 g carbohydrate) consumed immediately following one of the four oral treatments: CON, 60 g water (control treatment); VIN, 25 g liquid vinegar (5% acidity; 1.25 g acetic acid) diluted with 35 g water; PILL, four vinegar tablets (1.50 g acetic acid) swallowed whole with 60 g water; and PILL-c, four crushed vinegar tablets dissolved in 60 g water. Capillary blood glucose was tested in the fasted state and at 30 and 60 minutes postmeal. Results. The 60-minute glucose excursion varied significantly by treatment (iAUC: 4.9 ± 0.6, 3.4 ± 0.4, 4.9 ± 0.6, and 4.1 ± 0.5 mmol˖h/l for CON, VIN, PILL, and PILL-c, respectively; F (3, 33) = 3.037, p = 0.043; repeated measures ANOVA). Post hoc analysis revealed a 31% reduction in the glucose postmeal excursion for VIN in comparison to CON and PILL ( p = 0.040 and p = 0.049, respectively). Conclusions. These data suggest that commercial vinegar tablets taken whole at mealtime are not as effective as liquid vinegar for reducing the postmeal glucose excursion in young, healthy adults.

A Review of Recent Findings on Meal Sequence: An Attractive Dietary Approach to Prevention and Management of Type 2 Diabetes

While adjustment of total energy and nutritional balance is critically important, meal sequence, a relatively simple method of correcting postprandial hyperglycemia, is becoming established as a practical dietary approach for prevention and management of diabetes and obesity. Meal sequence, i.e., consumption of protein and/or fat before carbohydrate, promotes secretion of glucagon-like peptide-1 (GLP-1) from the gut and ameliorates secretions of insulin and glucagon and delays gastric emptying, thereby improving postprandial glucose excursion. GLP-1 is known to suppress appetite by acting on the hypothalamus via the afferent vagus nerve. Thus, enhancement of GLP-1 secretion by meal sequence is expected to reduce body weight. Importantly, consumption of a diet rich in saturated fatty acids such as meat dishes before carbohydrate increases secretions of not only GLP-1 but also glucose-dependent insulinotropic polypeptide (GIP), which promotes energy storage in adipose tissue and may lead to weight gain in the long term. Dietary fiber intake before carbohydrate intake significantly reduces postprandial glucose elevation and may have a weight loss effect, but this dietary strategy does not enhance the secretion of GLP-1. Thus, it is suggested that their combination may have additive effects on postprandial glucose excursion and body weight. Indeed, results of some clinical research supports the idea that ingesting dietary fiber together with meal sequence of protein and/or fat before carbohydrate benefits metabolic conditions of individuals with diabetes and obesity.

MON-028 Chronic Resveratrol Exposure Improves Glucose Homeostasis and Cardiac Function in a Rat Model of Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age, with a prevalence of 5-8%. Long-term complications seen in PCOS include cardiovascular disease and type 2 Diabetes Mellitus. Current therapies do not completely address the cardiometabolic perturbations seen in women with PCOS. Resveratrol (RSV), a natural polyphenol, is shown to have beneficial cardio-metabolic effects in various pathological conditions including that on insulin sensitivity, cardiovascular function. In-vitro studies suggest it’s beneficial effects on ovarian function as well. Therefore, we hypothesized that chronic exposure to RSV would improve both cardiovascular and metabolic phenotypes in PCOS. To test this hypothesis we used an established rat model of PCOS that develops metabolic derangement and irregular cycles. A 7.5 mg (90-day release) dihydrotestosterone (DHT) pellet providing a daily dose of 83 mcg was implanted in 5-week-old female rats. Studies were also conducted on littermate matched controls (C) with no DHT implant. A subgroup of the control and DHT treated rats (n=6 per group) received a 0.84 g/kg dose of resveratrol (RSV) in their chow starting at age 5 weeks. At 8 weeks, animals were weighed weekly (n=6 per group). Oral glucose tolerance test (OGTT n=6 per group) and cardiac echocardiogram (C n=12, C+RSV n=6, DHT n=10, DHT+RSV n=6) were conducted at 16-weeks of age. Body weight increased significantly in DHT treated rats compared to C between 8 and 16 weeks (40 vs 22 grams, p &lt;0.001). RSV treatment did not mitigate the effects of DHT on body weight (34 vs 40 grams, p&gt;0.5). There was significantly higher glucose excursion at 30 minutes post glucose load in both DHT (148± 7.4 mg/dl) and DHT+RSV (139± 7.4 mg/dl) compared to C group (121± 13 mg/dl, p&lt;0.001, p=0.03 respectively). However, by 60 and 90 minutes only DHT group had a significantly higher glucose excursion compared to both DHT+RSV and C groups (131± 4.1,124± 5.7,110 ± 5.9 mg/dl, p=0.015,p=0.21 respectively); 90min (118±5.8,110±4.7,96±4.2 mg/dl, p&lt;0.01,p=0.09 respectively). By 120 minutes, no significant difference in glucose levels existed between groups. Cardiac echocardiogram showed significantly lower mitral valve E/A ratio (and increased MV isovolumic relaxation time (IVRT) in DHT group compared to C. RSV treatment reversed these changes. In conclusion, RSV improved glucose homeostasis and diastolic dysfunction in the DHT induced rodent model of PCOS and may serve as a novel treatment option targeting the cardiometabolic derangement seen in PCOS. Further studies elucidating the mechanisms underlying the beneficial effects of RSV on cardio-metabolic phenotype in this PCOS rodent model is warranted.

Effects of Exercise on Blood Glucose and Glycemic Variability in Type 2 Diabetic Patients with Dawn Phenomenon

Background. The dawn phenomenon (DP) is the primary cause of difficulty in blood glucose management in type 2 diabetic (T2D) patients, and the use of oral hypoglycemic agents has shown weak efficacy in controlling DP. Thus, this study is aimed at investigating the effect of moderate-intensity aerobic exercise before breakfast on the blood glucose level and glycemic variability in T2D patients with DP. Methods. A total of 20 T2D patients with DP confirmed via continuous glucose monitoring (CGM) participated in the current study. After collecting baseline measurements by CGM as a control, CGM was reinstalled and 30 minutes of moderate-intensity aerobic exercise was performed prior to breakfast. Dawn blood glucose increase, blood glucose levels, and glycemic variability were measured before and after exercise. Results. Dawn blood glucose increase (ΔGlu, 1.25±0.84vs.2.15±1.07, P=0.005), highest blood glucose value before breakfast (Gmax, 8.01±1.16vs. 8.78±1.09, P=0.005), and mean blood glucose (MBG, 7.80±0.97vs. 8.37±0.95, P=0.001) were all lower, and time in range (TIR, 90.75±12.27vs. 83.5±15.41, P=0.015) was higher after exercise than before exercise. Among the glycemic variability indicators, blood glucose standard deviation (SD, 1.1±0.5vs. 1.48±0.63, P=0.001), coefficient of variation (CV, 14.14±5.94vs.17.69±7.46, P=0.006), mean amplitude of glucose excursion (MAGE, 2.71±1.52vs.3.73±1.98, P=0.006), and largest amplitude of glucose excursion (LAGE, 4.97±2.07vs.6.41±2.36, P=0.002) were all decreased following exercise. Conclusions. Acute moderate-intensity aerobic exercise before breakfast reduced the morning rise of blood glucose in T2D patients, partially counteracting DP. Furthermore, exercise significantly reduced blood glucose fluctuations and improved blood glucose control throughout the day. We recommend that T2D patients with DP take moderate-intensity aerobic exercise before breakfast to improve DP and glycemic control.