Clinical application of real-time continuous glucose monitoring system during postoperative enteral nutrition therapy in esophageal cancer patients.

BACKGROUND: Enteral nutrition (EN) support therapy increases the risk of abnormal blood glucose (BG). The aim of this study is to evaluate the clinical value of a real-time continuous glucose monitoring (rt-CGM) system in BG monitoring during postoperative EN support therapy in patients with esophageal cancer. METHODS: Patients without diabetes mellitus (DM) with esophageal cancer who planned to receive postoperative EN were enrolled. With the self-monitoring of BG value as the reference BG, the accuracy of rt-CGM was evaluated by the mean absolute relative difference (MARD) value, correlation efficient, agreement analysis, and Parkes and Clarke error grid plot. Finally, paired t tests were used to compare the differences in glucose fluctuations between EN and non-EN days and slow and fast days. RESULTS: The total MARD value of the rt-CGM system was 13.53%. There was a high correlation between interstitial glucose and fingertip capillary BG (consistency correlation efficient = 0.884 [95% confidence interval, 0.874-0.894]). Results of 15/15%, 20/20%, 30/30% agreement analysis were 58.51%, 84.71%, and 99.65%, respectively. The Parkes and Clarke error grid showed that the proportion of the A and B regions were 100% and 99.94%, respectively. The glucose fluctuations on EN days vs non-EN days and on fast days vs slow days were large, and the difference was statistically significant (P < 0.001). CONCLUSION: The rt-CGM system achieved clinical accuracy and can be used as a new option for glucose monitoring during postoperative EN therapy. The magnitude of glucose fluctuation during EN therapy remains large, even in the postoperative population without DM.

The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

Long-Term Effects and Potential Impact of Early Nutrition with Breast Milk or Infant Formula on Glucose Homeostasis Control in Healthy Children at 6 Years Old: A Follow-Up from the COGNIS Study.

There is scarce evidence about early nutrition programming of dynamic aspects of glucose homeostasis. We analyzed the long-term effects of early nutrition on glycemic variability in healthy children. A total of 92 children participating in the COGNIS study were considered for this analysis, who were fed with: a standard infant formula (SF, n = 32), an experimental formula (EF, n = 32), supplemented with milk fat globule membrane (MFGM) components, long-chain polyunsaturated fatty acids (LC-PUFAs), and synbiotics, or were breastfed (BF, n = 28). At 6 years old, BF children had lower mean glucose levels and higher multiscale sample entropy (MSE) compared to those fed with SF. No differences in MSE were found between EF and BF groups. Normal and slow weight gain velocity during the first 6 months of life were associated with higher MSE at 6 years, suggesting an early programming effect against later metabolic disorders, thus similarly to what we observed in breastfed children. Conclusion: According to our results, BF and normal/slow weight gain velocity during early life seem to protect against glucose homeostasis dysregulation at 6 years old. EF shows functional similarities to BF regarding children's glucose variability. The detection of glucose dysregulation in healthy children would help to develop strategies to prevent the onset of metabolic disorders in adulthood.

Treating to Target Glycaemia in Type 2 Diabetes Pregnancy.

There is an increasing awareness that in those who develop early-onset (18-39 years) adult type 2 diabetes, an increase in insulin resistance, deterioration in beta-cell, and clustering of cardiovascular risk factors are particularly pronounced. Pregnant women with type 2 diabetes have additional risk factors for serious adverse pregnancy outcomes as well as added barriers regarding healthcare access before, during, and after pregnancy. Compared to pregnant women with type 1 diabetes, those with type 2 diabetes are older, have higher body mass index (BMI), with more metabolic comorbidities and concomitant medications, are more likely to belong to minority ethnic groups, and live in the highest areas of socio-economic deprivation. Approximately, one in seven pregnant women with type 2 diabetes (median age 34 years) are taking ACE-inhibitors, statins (13%), and/or other potentially harmful diabetes therapies (7%). Fewer than one in four are taking a high dose of folic acid before pregnancy, which may suggest that planning for pregnancy is not a priority for women themselves, their healthcare professionals, or the healthcare system. Knowledge of the epidemiology, pathophysiology, and unique management considerations of early-onset type 2 diabetes is essential to providing evidence-based care to pregnant women with type 2 diabetes. This narrative review will discuss contemporary data regarding type 2 diabetes pregnancy outcomes and the increasing recognition that different types of diabetes may require different treatment strategies before, during, and after pregnancy.

Impact of super energy-dense oral nutritional supplementation (SED ONS) on glycemic variability and food intake postoperatively in gastric cancer patients.

PURPOSE: Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy. METHODS: Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve < glucose 70 mg/dL (AUC < 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake. RESULTS: Seventeen patients were enrolled. The AUC < 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided. CONCLUSION: SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.

Insulin delivery patterns required to maintain postprandial euglycemia in type 1 diabetes following consumption of traditional Egyptian Ramadan Iftar meal using insulin pump therapy: A randomized crossover trial.

OBJECTIVES: During Ramadan, traditional Egyptian Iftar meals have large amounts of high-glycemic index carbohydrate and fat. The efficacy of different bolus regimens on optimizing post prandial glucose (PPG) excursion following this Iftar meal was assessed. METHODS: A randomized controlled trial evaluating 4-h PPG measured by continuous glucose-monitoring was conducted. A total of 25 youth with T1DM using insulin pumps were given the same Iftar meal (fat [45 g], protein [28 g], CHO [95 g]) on seven consecutive days. Insulin to carbohydrate ratio (ICR) was individualized, and all boluses were given upfront 20 min before Iftar. Participants were randomized to receive a standard bolus and six different split boluses delivered over 4 h in the following splits: dual wave (DW) 50/50; DW 50/50 with 20% increment (120% ICR); DW60/40; DW 60/40 with 20% increment; DW 70/30 and DW 70/30 with 20% increment. RESULTS: Standard bolus and split 70/30 with 20% increment resulted in significantly lower early glucose excursions (120 min) with mean excursions of less than 40 mg/dL (2.2 mmol/L) compared to other conditions (p < 0.01). The split 70/30 with 20% increment significantly optimized late PPG excursion (240 min) in comparison to standard bolus (p < 0.01), as well as resulting in a significantly lower post meal glucose area under the curve compared with all other conditions (p < 0.01), with no late hypoglycemia. CONCLUSION: To achieve physiologic PPG profile in traditional Iftar meal, a DW bolus with 20% increment given 20 min preprandial as split bolus 70/30 over 4 h, optimized both early and delayed PPG excursions.

Demonstrating the Clinical Impact of Continuous Glucose Monitoring Within an Integrated Healthcare Delivery System.

BACKGROUND: Approximately 30 million Americans currently suffer from diabetes, and nearly 55 million people will be impacted by 2030. Continuous glucose monitoring (CGM) systems help patients manage their care with real-time data. Although approximately 95% of those with diabetes suffer from type 2, few studies have measured CGM's clinical impact for this segment within an integrated healthcare system. METHODS: A parallel randomized, multisite prospective trial was conducted using a new CGM device (Dexcom G6) compared to a standard of care finger stick glucometer (FSG) (Contour Next One). All participants received usual care in primary care clinics for six consecutive months while using these devices. Data were collected via electronic medical records, device outputs, exit surveys, and insurance company (SelectHealth) claims in accordance with institutional review board approval. RESULTS: Ninety-nine patients were randomized for analysis (n = 50 CGM and n = 49 FSG). CGM patients significantly decreased hemoglobin A1c (p = .001), total visits (p = .009), emergency department encounters (p = .018), and labs ordered (p = .001). Among SelectHealth non-Medicare Advantage patients, per member per month savings were $417 for CGM compared to FSG, but $9 more for Medicare Advantage. Seventy percent of CGM users reported that the technology helped them better understand daily activity and diet compared to only 16% for FSG. DISCUSSION: Participants using CGM devices had meaningful improvements in clinical outcomes, costs, and self-reported measures compared to the FSG group. Although a larger study is necessary to confirm these results, CGM devices appear to improve patient outcomes while making treatment more affordable.

Glycerol Potentiates the Effects of Glucose in Promoting Glucose Recovery During Hypoglycemia: From Basic to Clinical Investigations and Their Therapeutic Application.

We compared the effect of oral glucose versus oral glucose combined with glycerol (glucose + glycerol) in promoting glucose recovery during hypoglycemia. These studies were carried out in two series of experiments. In the first series of experiments, 16 overnight fasted rats received an intraperitoneal injection of lispro insulin (1 IU/kg), and 25 min later, they received oral water (control), glucose (0.25 g/kg), glycerol (2.5 g/kg), or glucose (0.25 g/kg) + glycerol (2.5 g/kg). In the second series of experiments on 164 eligible type 1 diabetic (T1D) patients, 30 individuals with a history of hypoglycemia were recruited. Five volunteers did not meet the inclusion criteria and two subjects were excluded after starting the clinical investigation; 23 patients concluded the study. All patients with symptoms of hypoglycemia ingested oral glucose (15 g) or glucose (15 g) + glycerol (9.45 g). To treat hypoglycemia in T1D patients, preparations containing glucose alone or glucose + glycerol were used alternately (2 weeks/2 weeks) in a double-blind crossover scheme. Throughout the clinical research (4 weeks), glucose concentrations were assessed with a continuous glucose monitoring device and the results after the use of glucose alone or glucose + glycerol preparations were compared. Oral glucose combined with glycerol was more effective in promoting glucose recovery in comparison with glucose alone, not only in rats but also in T1D patients. Taken together, our experimental and clinical investigations reported the best performance of oral administration of glucose + glycerol in comparison with isolated glucose.

Effect of Lupin-Enriched Biscuits as Substitute Mid-Meal Snacks on Post-Prandial Interstitial Glucose Excursions in Post-Surgical Hospital Patients with Type 2 Diabetes.

Hospital biscuit snacks offered to Type 2 Diabetes Mellitus (T2DM) patients may adversely affect glycaemic control. This study investigated the effect of lupin mid-meal biscuit snacks, compared to spelt or standard hospital biscuits, on interstitial glucose levels in post-operative T2DM inpatients. In a pilot cross-over pragmatic study, 20 patients (74 ± 12 years) consumed, in order, lupin biscuits (20% lupin), wholemeal spelt and standard plain sweet biscuits as mid-meal snacks (2 biscuits each for morning and afternoon tea) on three consecutive days. Continuous glucose monitoring, appetite perceptions and bowel motions were recorded. Glucose levels were not significantly different in the first 90 min after mid-meal biscuit consumption at morning and afternoon tea, irrespective of type. However, after consuming the lupin biscuits only, glucose levels were significantly (p < 0.001) reduced 90 min postprandially after dinner, indicating a potential second-meal effect. Patients also reported improved satiety after lupin biscuit consumption on day 1, compared to days 2 and 3 (p = 0.018). These findings suggest that lupin-enriched biscuits may improve both glycaemic control and satiety in hospitalised T2DM patients, potentially contributing to reduced length of stay. Larger controlled studies are warranted to confirm these findings and inform potential revision of hospital menu standards for T2DM patients.

Safety of a continuous glucose monitoring device during hyperbaric exposure.

Background: Hyperbaric oxygen therapy has been demonstrated to lower blood glucose levels in patients with diabetes. Continuous glucose monitoring (CGM) allows glucose monitoring in real time. Battery-operated CGM transmitters have yet to be formally tested and given safety approval for use in a hyperbaric environment. Materials and Methods: We evaluated and tested commercially available Dexcom® G6 CGM transmitters under hyperbaric conditions. Each transmitter contains a 3V, 130-mAh (0.39 Wh) lithium manganese dioxide battery (IEC CR1632) and circuit board that are fully encapsulated in epoxy. Each transmitter is pressurized to 90 pounds per square inch (psi) in an autoclave at 40°C for up to 72 hours during manufacturing to ensure that all enclosed air spaces are eliminated from the epoxy. We compared the CGM components against section 14.2.9.3.17.5 of the 2018 National Fire Protection Association 99 (NFPA 99) Health Care Facilities Code requirements. Six CGM transmitters attached to estimated glucose value generators (EGVGs) underwent 11 pressurization cycles to 45 feet of seawater (fsw). All transmitters were returned to the manufacturer to assess post-exposure structural integrity. G6 sensors, which contain no electrical components or compressible air spaces, do not pose a risk in the hyperbaric environment. Results: There was no observed change in preset EGVG readings during hyperbaric exposures. Post-exposure testing revealed no structural compromise after repeated hyperbaric exposures. Conclusions: The CGM transmitter meets section 14.2.9.3.17.5 of the 2018 NFPA 99 requirements for battery-operated devices allowed for use in a hyperbaric environment. This analysis revealed no significant safety concerns with subjecting Dexcom G6 CGM transmitters to hyperbaric environments.

Postprandial hypoglycaemia after Roux-en-Y gastric bypass and the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide.

AIM: To investigate the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide on post-bariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass. MATERIALS AND METHODS: In a randomized crossover study, 11 women who had undergone Roux-en-Y gastric bypass and had documented hypoglycaemia were each evaluated during a baseline period without treatment and during five treatment periods with the following interventions: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks and pasireotide 300 µg as a single dose. Treatment effects were evaluated by a mixed-meal tolerance test (MMTT) and, for all treatment periods except pasireotide, by 6 days of continuous glucose monitoring (CGM). RESULTS: Treatment with acarbose and treatment with pasireotide both significantly lifted nadir glucose levels (mean ± SEM 3.9 ± 0.2 and 7.9 ± 0.4 vs 3.4 ± 0.2; P < .03) and reduced time in hypoglycaemia during the MMTTs. Acarbose reduced peak glucose levels and time in hyperglycaemia, whereas pasireotide greatly increased both variables. Acarbose and pasireotide reduced insulin and C-peptide levels, and pasireotide also diminished glucagon-like peptide-1 levels. Sitagliptin lowered nadir glucose values, while verapamil and liraglutide had no effect on hypoglycaemia. During the CGM periods, the treatments had no impact on hypoglycaemia, whereas acarbose and liraglutide reduced hyperglycaemia and glycaemic variability. CONCLUSIONS: In an experimental setting, treatment with acarbose and pasireotide reduced PBH. Acarbose appears to have an overall glucose-stabilizing effect, whereas pasireotide leads to increased and sustained hyperglycaemia.

Fibre-enriched buckwheat pasta modifies blood glucose response compared to corn pasta in individuals with type 1 diabetes and celiac disease: Acute randomized controlled trial.

AIM: People with type 1 diabetes and celiac disease (T1D&CD) have high blood glucose variability. Processed gluten-free foods have shown to induce a worse metabolic profile whereas naturally gluten-free foods may represent healthier options. On the other hand, dietary fibre has shown to reduce postprandial glycemic excursions in individuals with diabetes. Thus, we evaluated the acute effect of fibre-enriched buckwheat (FBP) and corn pasta (CP) on postprandial blood glucose response (PP-BGR). METHODS: Ten adult patients with T1D&CD consumed two meals with the same amount of carbohydrate while differing only for pasta type (FBP or CP) preceded by the same insulin bolus. Participants utilized continuous glucose monitoring (CGM) and data over 6 h after meal were analyzed. RESULTS: PP-BGR differed between the two meals, being significantly lower in the first period (0-3 h) after the CP than the FBP meal (iAUC: -38 ±â€¯158 vs. 305 ±â€¯209 mmol/L ·â€¯180 min, p = 0.040), whereas significantly higher in the second period (3-6 h) after the CP than the FBP meal (iAUC: 432 ±â€¯153 vs. 308 ±â€¯252 mmol/L ·â€¯180 min, p = 0.030). Overall, a less variable postprandial profile was observed after FBP than CP consumption. CONCLUSIONS: In individuals with T1D&CD, the acute consumption of FBP induces significant differences in PP-BGR compared with CP that may be clinically relevant.

Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: Findings of a randomized cross-over trial.

AIM: The primary aim of this study was to investigate whether ascorbic acid (AA) supplementation improves postprandial glucose responses under free-living conditions in individuals with type 2 diabetes. A secondary aim was to investigate the effect of AA supplementation on blood pressure. MATERIALS AND METHODS: A total of 31 individuals with type 2 diabetes (26 males and 5 females; aged 61.8 ± 6.8 years; duration of diabetes, 5.6 ± 4.6 years; HbA1c, 7.6% ± 0.7% [mean ± SD]) were enrolled in a randomized cross-over study involving 4 months of supplementation with oral AA (2 × 500 mg/d) or placebo. Participants wore continuous glucose monitors for 48 hours and consumed standardized meals pre- and post-supplementation. Measurements included postprandial glucose incremental areas under the curve (iAUC), duration of day in hyper- and hypo-glycaemia status, average 24-hour and daily postprandial glucose concentrations, HbA1c, insulin, blood pressure (BP) and oxidative stress (F2 -isoprostanes). RESULTS: Following AA supplementation, significant decreases were observed in daily postprandial glucose iAUC (-36%), in duration of day with hyperglycaemia (-2.8 h/d) and postprandial hyperglycaemia (-1.7 h/d), in average 24-hour glucose (-0.8 mmol/L) and daily postprandial glucose (-1.1 mmol/L) concentrations, in systolic (-7 mm Hg) and diastolic (-5 mm Hg) blood pressures and in a specific fraction of free plasma F2 -isoprostanes (-47 pg/mL) as compared to placebo. CONCLUSIONS: Individuals with type 2 diabetes experienced improved postprandial and 24-hour glycaemia and decreased BP after 4 months of AA supplementation as compared to placebo. These findings offer evidence for the proposed use of AA as an adjunct therapy to improve glycaemic and BP control in individuals with type 2 diabetes.

Glycemic excursions are positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy.

BACKGROUND: The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). METHODS: Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100. RESULTS: Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (ß = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P < 0.05 for all models). CONCLUSIONS: In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D.

Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes.

AIM: The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). METHODS: Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. RESULTS: A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (ß coefficient 0.345, p=0.036) or acarbose (ß coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). CONCLUSIONS: Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Hypoglycaemia after gastric bypass: mechanisms and treatment.

Hypoglycaemia after gastric bypass can be severe, but is uncommon, and is sometimes only revealed through monitoring glucose concentrations. The published literature is limited by the heterogeneity of the criteria used for diagnosis, arguing in favour of the Whipple triad with a glycaemia threshold of 55 mg/dl as the diagnostic reference. Women who lost most of their excess weight after gastric bypass, long after the surgery was performed, and who did not have diabetes before surgery are at the greatest risk. In this context, hypoglycaemia results from hyperinsulinism, which is either generated by pancreas anomalies (nesidioblastosis) and/or caused by an overstimulation of ß cells by incretins, mainly glucagon-like peptide-1 (GLP-1). Glucose absorption is both accelerated and increased because of the direct communication between the gastric pouch and the jejunum. This is a post-surgical exaggeration of a natural adaptation that is seen in patients who have not undergone surgery in whom glucose is infused directly into the jejunum. There is not always a correspondence between symptoms and biological traits; however, hyperinsulinism is constant if hypoglycaemia is severe and there are neuroglucopenic symptoms. The treatment relies firstly on changes in eating habits, splitting food intake into five to six daily meals, slowing gastric emptying, reducing the glycaemic load and glycaemic index of foods, using fructose and avoiding stress at meals. Pharmacological treatment with acarbose is efficient, but other drugs still need to be validated in a greater number of subjects (insulin, glucagon, calcium channel blockers, somatostatin analogues and GLP-1 analogues). Lastly, if the surgical option has to be used, the benefits (efficient symptom relief) and the risks (weight regain, diabetes) should be weighed carefully.

Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial.

BACKGROUND & AIMS: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. METHODS: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system (CGMS)) were recorded throughout the intervention period. RESULTS: Following the 12-week trial subjects receiving the IEB exhibited a significant decrease in insulin, HOMA-IR and Apo B and an increase in LDL particle size, whereas the SB group showed increases in BMI and fasting glucose concentration. Analysis of postprandial glucose levels at breakfast, lunch and dinner revealed a mean reduction of glucose of ≈14% and a significant reduction in the area under the curve at 24 h after consumption of the IEB. CONCLUSIONS: Our results show that chronic IEB supplementation induces a significant improvement in carbohydrated metabolism parameters in healthy subjects.

Effect of Acarbose on Glycemic Variability in Patients with Poorly Controlled Type 2 Diabetes Mellitus Receiving Stable Background Therapy: A Placebo-Controlled Trial.

STUDY OBJECTIVE: To evaluate the effect of acarbose on glycemic control and glycemic variability, using a continuous glucose-monitoring system, in patients with type 2 diabetes mellitus who were not well controlled on metformin and vildagliptin therapy. DESIGN: Multicenter, randomized, double-blind, placebo-controlled study. SETTING: Clinical research units at three hospitals in Italy. PATIENTS: Fifty-three patients with type 2 diabetes who were taking stable dosages of metformin 850 mg 3 times/day and vildagliptin 50 mg twice/day for at least 3 months and who were not adequately controlled with these therapies. INTERVENTION: Patients were randomized to either placebo or acarbose 100 mg 3 times/day to be added to their metformin-vildagliptin regimen. MEASUREMENTS AND MAIN RESULTS: Glycemic excursions were assessed by using a continuous glucose-monitoring system for 1 week. Glycemic control was estimated as the mean blood glucose (MBG) level, the area under the glucose concentration-time curve for a glucose level above 70 mg/dl (AUC above 70) or 180 mg/dl (AUC above 180), and the percentage of time that the glucose level was above 70 mg/dl (T above 70) or 180 mg/dl (T above 180). Intraday glycemic variability was assessed by the standard deviation of the blood glucose level, the mean amplitude of glycemic excursions (MAGE), the M value, and continuous overlapping net glycemic action. Day-to-day glycemic variability was assessed as the mean of daily difference (MODD). The MBG level was ~20 mg/dl lower in the acarbose group than in the placebo group (p<0.05), particularly during the postprandial period. The AUC above 70 did not significantly differ between the two groups, whereas the AUC above 180 was ~40% lower in the acarbose group than in the placebo group during the daytime (p<0.01). The T above 180 was significantly higher in the placebo group than in the acarbose group (31% vs 8%, p<0.01. Moreover, the standard deviation and MAGE values were significantly lower in the acarbose group. The MODD value was not significantly changed in either group, and no significant differences were recorded between groups. All adverse events were mild in both groups, with only a significantly greater frequency of flatulence noted in the acarbose group (5% with acarbose vs 0.5% with placebo, p<0.05). CONCLUSION: The addition of acarbose to metformin and vildagliptin background therapy in patients with inadequately controlled type 2 diabetes decreased intraday glycemic variability, especially postprandial variability, but it was not associated with a significant change in interday glycemic variability.

Association between post-dinner dietary intakes and nocturnal hypoglycemic risk in adult patients with type 1 diabetes.

AIMS: To describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs. METHODS: One hundred adults (median [interquartile range]: age 46.4 [36.0-55.8] years, HbA1c 7.9 [7.3-8.6] % (63 [56-70] mmol/mol)) using multiple daily injections (n=67) or insulin pump (n=33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h. RESULTS: NH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n=37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04-1.29] per 5g increase, p=0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78-1.00] per 2g increase, p=0.048). CONCLUSIONS: NH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation.

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study.

OBJECTIVE: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. METHODS: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. RESULTS: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. CONCLUSION: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.