Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon-like peptide-1, and gastric emptying after oral glucose, in type 2 diabetes.

AIMS: The gastrointestinal tract, particularly the lower gut, may be key to the anti-diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM). MATERIALS AND METHODS: Ten diet-controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg 13 C-acetate. "Arterialized" venous blood and breath samples were collected over 3 hours for measurements of plasma glucose, GLP-1, insulin and glucagon, and GE, respectively. RESULTS: Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP-1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin. CONCLUSIONS: In diet-controlled T2DM patients, glucose-lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP-1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose-lowering capacity of metformin.

Correlation Between the First Trimester Two-Hour Postprandial Blood Glucose Greater Than 110 mg/dL for the Prediction of Gestational Diabetes Mellitus.

AIM: To determine the correlation between first-trimester two-hour postprandial blood glucose (PPBG) > 110 mg/dL for predicting gestational diabetes mellitus (GDM). METHODS: This prospective cohort study enrolled 200 women between 8 and 10 weeks of gestation from February 2022 to February 2024. All recruited pregnant women underwent testing for two-hour PPBS at 8-10 weeks and were followed up till delivery. GDM screening was done during 14-16, 24-28, and 32-34 weeks of gestation. RESULTS: Amongst women having PPBS > 110 mg/dL, 95.9% developed GDM, while in the group with PPBS < 110 mg/dL, only 4% developed GDM. In the PPBS > 110 mg/dL group, a significantly higher number of women were in the older age group (p < 0.049), had a higher BMI (p < 0.001), a family history of diabetes (p < 0.001), and previous history of abortion (p < 0.001). Women with PPBS > 110 mg/dL had significantly higher rates of cesarean section (p < 0.01), preterm delivery (p < 0.001), and macrosomia (p < 0.001). A positive correlation (r = 0.677; p < 0.001) was observed between first trimester two-hour PPBS and cord blood glucose levels. Similarly, a positive correlation (r = 0.465; p < 0.001) was present between insulin levels measured during the first trimester with cord blood insulin. The area under the curve (AUC) for PPBS was 0.969 (p < 0.001) with 95% CI: 0.933-0.988. PPBS > 110 mg/dL has a sensitivity of 95.9%, specificity of 95.6%, positive predictive value (PPV) of 95.9%, negative predictive value (NPV) of 95.7%, and diagnostic accuracy of 95.77% to predict GDM. CONCLUSION: PPBS > 110 mg/dL at two hours exhibits high levels of diagnostic accuracy for the prediction of GDM and is associated with adverse fetomaternal outcomes. PPBG is a superior, physiologic, and low-cost option compared to HbA1c for early prediction of GDM and can also be performed as a simple point-of-care test with a glucometer at home or in the periphery by healthcare workers (HCW) and in wellness centers.

Optimal Prandial Timing of Insulin Bolus in Youths with Type 1 Diabetes: A Systematic Review.

The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002-2022). A PICOS framework was used in the selection process and evidence was assessed using the GRADE system. Up to one third of children and adolescents with type 1 diabetes injected rapid-acting insulin analogues after a meal. Moderate-high level quality studies showed that a pre-meal bolus compared with a bolus given at the start or after the meal was associated with a lower peak blood glucose after one to two hours, particularly after breakfast, as well as with reduced HbA1c, without any difference in the frequency of hypoglycemia. There were no differences related to the timing of bolus in total daily insulin and BMI, although these results were based on a single study. Data on individuals' treatment satisfaction were limited but did not show any effect of timing of bolus on quality of life. In addition, post-prandial administration of fast-acting analogues was superior to rapid-acting analogues on post-prandial glycemia. There was no evidence for any difference in outcomes related to the timing of insulin bolus across age groups in the two studies. In conclusion, prandial insulin injected before a meal, particularly at breakfast, provides better post-prandial glycemia and HbA1c without increasing the risk of hypoglycemia, and without affecting total daily insulin dose and BMI. For young children who often have variable eating behaviors, fast-acting analogues administered at mealtime or post-meal could provide an additional advantage.

Improved time in range and postprandial hyperglycemia with canagliflozin in combination with teneligliptin: Secondary analyses of the CALMER study.

AIMS/INTRODUCTION: We recently reported the beneficial effect of the combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis. MATERIALS AND METHODS: The CALMER study was a multicenter, open-label, prospective, randomized, parallel-group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated. RESULTS: All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2-82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (-14.8% vs -7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group (P < 0.05). CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase-4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy.

Adherence to Treatment and Glycemic Control in Patients with Type 2 Diabetes Mellitus: A 4-Year Follow-up PTM Bogor Cohort Study, Indonesia.

PURPOSE: Large-scale evaluation of the treatment adherence in patients with type 2 diabetes mellitus (DM) in Indonesian is limited. We aim to evaluate the treatment adherence of Indonesian type 2 DM patients using national "big data" and investigate its association with glycemic parameters. PATIENTS AND METHODS: We analyzed baseline and fourth-year data sets from 2011 to 2018 obtained from the Indonesian Ministry of Health Cohort Study of Non-Communicable Disease Risk Factors in Bogor, West Java (the PTM Bogor Cohort Study). This was a retrospective cohort study in which the sample was divided into two groups. One group adhered to treatment from primary health centers and followed the prescribed medicine/treatment regimen (treated group), while the other did not follow the treatment (untreated group). We evaluated changes in fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) by controlling for other variables. RESULTS: From 5690 subjects, 593 were type 2 DM diagnosed and 342 were eligible at the baseline. At 4-year observation, 212 eligible patients remained, consisting of 62 subjects who adhered to treatment, and more than double that number who were untreated (150 subjects). More significant decreases in FBG and PPBG were found in the treated group (FBG 80.6%, PPBG 90.3%) than in the untreated group (FBG 42.0%, PPBG 67.3%). The results of the multivariate analysis showed that after 4 years observation, treated patients have reduced FBG 3.304 times more and PPBG 3.064 times more than untreated patients, with control factors such as decrease in LDL levels and use of oral drugs. CONCLUSION: There were less than half as many treated patients as untreated patients involved in the PTM Bogor Study Group. At the fourth-year follow-up, treated patients experienced three times more significant decreases in FBG and PPBG than those who were untreated, even after being controlled by several confounding factors. Given the importance of these findings, it is suggested that immediate strategic action be taken to improve Indonesian patients' adherence to treatment.

Diabetes induced renal complications by leukocyte activation of nuclear factor κ-B and its regulated genes expression.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

Blood glucose response to a calamansi drink in healthy adults: a non-randomised study.

OBJECTIVE: Glycaemic Index (GI) ranks the body's response to carbohydrate content in food such that high GI food increases postprandial blood glucose levels. One of the popular drinks at food and beverage outlets is a drink made from calamansi, a citrus that is believed not to induce an increase in blood glucose levels. In this non-randomised single-blind (participants) study, capillary blood from 10 healthy males were sampled following consumption of either glucose or the calamansi drink. The blood glucose measurements were then used to calculate the GI for the drink. RESULTS: The GI of the calamansi drink tested was calculated as 37, a value within the range of low GI foods. Trial registration Clinical Trials identifier NCT04462016; Retrospectively registered on July 1, 2020.

Preliminary clinical assessment and non- toxicity evaluation of an ayurvedic formulation BGR-34 in NIDDM.

In view of the overall health impact of NIDDM, inventers understand the necessity of improving glycemic control in adults with type 2 diabetes. BGR-34 provides an effective treatment option for adults with type 2 diabetes who have been inadequately controlled on lifestyle with or without other oral hypoglycemic agents (OHGAs) such as metformin, sulfonylurea, or a glitazones. BGR-34 is an appropriate option to consider for addition to a managed care drug formulary. Treatment with BGR-34 produced clinically relevant and statistically significant reductions in all three key measures of glucose control studied -FPG, PPBG and HbA1c- when compared with placebo. BGR-34, showed the promising result with respect to glycemic parameters in NIDDM patient with a significant reduction in fasting blood sugar by 34.3%, postprandial blood sugar 35.5% & glycosylated haemoglobin by 20.31% as compared to placebo group showing a reduction by 13.2%, 10.9% & 10.87% respectively. The trial has also been registered to CTRI, India. This study has been registered in the clinical trial registry-India.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients.

BACKGROUND: Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. METHODS: Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. RESULTS: A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. CONCLUSION: We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Effect of increasing duration of diabetes mellitus type 2 on glycated hemoglobin and insulin sensitivity.

Non-insulin dependent diabetes mellitus (NIDDM) is the most rapidly growing chronic metabolic disorder in the world. With advancement in the age and duration of diabetes there is a gradual tendency for the level of blood sugar to rise along with a subsequent increase in the HbA1c as well as in the fasting insulin level. Whether this is an aging process or increased frequency of diabetes is still controversial. The correlation between glucose and insulin sensitivity is consistent with the idea that the degree of chronic hyperglycemia is a cause of excessive insulin resistance in type 2 diabetes, i.e. the insulin resistance which characterizes type 2 diabetes but not nondiabetic subjects matched for age, gender, family history and duration of diabetes. The study comprised a total of 76 subjects out of which 30 were normal, non-diabetic persons and the rest 46 were diabetics with different duration of time in years, after being diagnosed diabetic. Data was analyzed after dividing the subjects into four groups-Group 1 comprised of one year old diabetics, Group 2 was made up of those, who had diabetes, for the past 2-5 years, Group 3 included patients who were diabetic since more than 5 years and Group 4 included non-diabetics as the normal control group. The results obtained indicated that the HbA1c levels showed a significant increase with the duration of diabetes as well as the insulin level showed a significant correlation after adjustment for age, sex and duration of diabetes.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

BACKGROUND: Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. METHODS: Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. RESULTS: A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. CONCLUSION: We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Effects of Resistant Maltodextrin on the on Post-Prandial Blood Glucose Elevation in Japanese Individuals / 医薬品情報学

<b>Objective: </b>We conducted a meta-analysis on the suppressive effect of resistant maltodextrin on post-prandial blood glucose elevation, which is approved in Japan as food for specified health use, and the following is allowed to be indicated on the label “it is suitable for consumption by those who are concerned about their post-prandial blood glucose levels because the absorption of sugars is abated by the action of dietary fiber (resistant maltodextrin).”<br><b>Method: </b>Our literature search covered Ichushi-Web (Japan Medical Abstracts Society), Japan Science and Technology Information Aggregator, Electronic (J-stage), Google Scholar, and PubMed databases and extracted English and Japanese publications on randomized, double-blind, controlled studies comparing resistant maltodextrin and a control in Japanese subjects for the reduction of areas under the blood glucose response curves at 30, 60, and 120 min after eating as an efficacy index.<br><b>Result: </b>Among these publications, four articles with a Jadad score (an assessment of the quality of randomized controlled studies) of ≥ 3 were included in the meta-analysis.  Significant inhibitory effects were confirmed from areas under the blood glucose response curves at 30, 60, and 120 min after eating in the meta-analysis that was performed to evaluate the effects of resistant maltodextrin on post-prandial blood glucose elevation in Japanese individuals.<br><b>Conclusion: </b>However, we were not able to test for publication bias because the number of extracted publications was small, and thus, additional research and case studies are warranted.

Respuesta de glucosa e insulina: Comparación entre dos tipos de desayunos y prueba de tolerancia oral con 75g. De glucosa

Objetivos: Comparar las respuestas glucémicas e insulinémicas de dos desayunos, con la prueba estándar de tolerancia a la glucosa oral (PTGO). Métodos: En 14 sujetos sanos se realizó la PTGO, con 75 gr de glucosa. Luego, con un intervalo de una semana, se efectuaron las pruebas de tolerancia con dos tipos de desayunos, elaborados con alimentos de uso común en nuestro medio y cuya principal diferencia fue el tipo de carbohidrato. A los 0, 30, 60 y 120 minutos se cuantificó la concentración de glucosa, por el método de glucosa-oxidasa y la insulina por radioinmunoanálisis. Se calculó el área bajo la curva para la respuesta de glucosa e insulina. Para el análisis estadístico se aplicó un análisis de varianza y las pruebas post-test, para determinar la diferencia entre los grupos. Resultados: Se observó que la respuesta de glucosa con el desayuno 1 fue significativamente menor (p<0,05) a los 30 y 60 minutos y con el desayuno 2 a los 60 minutos (p<0.05) en comparación con la obtenida con la PTGO. El área bajo la curva (ABC) de glucemia no fue diferente entre los 2 tipos de desayunos y fue significativamente menor que con la PTGO. La respuesta de insulina fue significativamente mas baja a los 120 minutos (p<0.05) con el desayuno 1 (arepa) en relación con el desayuno 2 (pan) y con la PTGO. El ABC de insulinemia no fue diferente entre los desayunos y la PTGO. Conclusiones: La respuesta de glucemia postprandial con mezcla de nutrientes es menor que la obtenida con la PTGO, por lo que no debe ser usada con fines diagnósticos.

Objectives: To compare the glycemic and insulinemic responses of two breakfasts with the standard oral glucose tolerance test (OGTT). Methods: In 14 healthy subjects, the OGTT with 75 g of glucose was performed. After an interval of one week, tolerance tests with two types of breakfasts elaborated with common food in our country, and whose main difference was the type of carbohydrate, were carried out. At 0, 30, 60 and 120 minutes, glucose concentration by the glucose oxidase method and insulin by radioimmunoassay were measured. Areas under the curve (AUC) for glucose and insulin response were calculated. An analysis of variance test was applied to determine the difference between the groups. Results: It was noted that the glucose response to breakfast 1 was significantly lower (p <0.05) at 30 and 60 minutes and to breakfast 2 at 60 minutes (p <0.05) compared with that obtained with OGTT. The glucose AUC was not different between the 2 types of breakfasts and was significantly lower than the obtained with OGTT. The insulin response was significantly lower at 120 minutes (p <0.05) with breakfast 1 (arepa) in relation to breakfast 2 (bread) and the OGTT. The insulin AUC was not different between breakfasts and the OGTT. Conclusions: The postprandial blood glucose response to mix of nutrients is lower than that obtained with the OGTT, so it should not be used for diagnostic purposes.