A Head-to-Head Comparison of Two Algorithms for Adjusting Mealtime Insulin Doses Based on CGM Trend Arrows in Adult Patients with Type 1 Diabetes: Results from an Exploratory Study.

BACKGROUND: Continuous glucose monitoring (CGM) users are encouraged to consider trend arrows before injecting a meal bolus. We evaluated the efficacy and safety of two different algorithms for trend-informed bolus adjustments, the Diabetes Research in Children Network/Juvenile Diabetes Research Foundation (DirectNet/JDRF) and the Ziegler algorithm, in type 1 diabetes. METHODS: We conducted a cross-over study of type 1 diabetes patients using Dexcom G6. Participants were randomly assigned to either the DirectNet/JDRF or the Ziegler algorithm for two weeks. After a 7-day wash-out period with no trend-informed bolus adjustments, they crossed to the alternative algorithm. RESULTS: Twenty patients, with an average age of 36 ± 10 years, completed this study. Compared to the baseline and the DirectNet/JDRF algorithm, the Ziegler algorithm was associated with a significantly higher time in range (TIR) and lower time above range and mean glucose. A separate analysis of patients on CSII and MDI revealed that the Ziegler algorithm provides better glucose control and variability than DirectNet/JDRF in CSII-treated patients. The two algorithms were equally effective in increasing TIR in MDI-treated patients. No severe hypoglycemic or hyperglycemic episode occurred during the study. CONCLUSIONS: The Ziegler algorithm is safe and may provide better glucose control and variability than the DirectNet/JDRF over a two-week period, especially in patients treated with CSII.

The Effect of Two Different Insulin Formulations on Postprandial Hyperglycemia after High and Low Glycemic-Index Meal in Type 1 Diabetes.

Despite multiple pharmacological options, including rapid-acting insulin analogs, postprandial hyperglycemia is still highly prevalent in patients with type 1 and type 2 diabetes. We hypothesize that the new rapid-acting insulin formulation, the so-called faster-acting Aspart, may have a different effect in controlling postprandial hyperglycemic burden according to the quality of the meal compared to the traditional Aspart. Twenty-five patients with type 1 diabetes were consecutively recruited at the diabetes care center of the University Hospital affiliate of the Magna Græcia University of Catanzaro. Each patient performed four meal tests one week apart, two with a predefined high glycemic index (HGI) food and two with a low glycemic index (LGI) food using insulin Aspart once and Faster Aspart the other time. The 0-30 min, 0-60 min, and 0-120 min glucose Area Under the Curve (AUC) of postprandial glycemic excursion, calculated from continuous glucose monitoring data, were significantly lower with Faster Aspart administered before the HGI test meal as compared to Aspart. A significant difference in favor of Faster Aspart was also found when comparing the 0-60 min and 0-120 min AUC after the LGI meal. Faster Aspart may provide better postprandial glucose control than Aspart regardless of the glycemic index of the meal.

Time spent in target range assessed by self-monitoring blood glucose associates with glycated hemoglobin in insulin treated patients with diabetes.

BACKGROUND AND AIMS: Self-monitoring blood glucose (SMBG) remains a widespread tool to monitor blood glucose. The development of diabetes management systems (DMS) allows SMBG to provide additional information as time spent in target range (TIR). This study evaluates the association between HbA1c and TIR, evaluated through DMS, over 2 months, and 2 weeks. METHODS AND RESULTS: Type 1 (T1D) and Type 2 (T2D) insulin-treated patients with diabetes were enrolled. We used the term PIR (Points in Range) instead of TIR, since SMBG provides point-in-time glucose values rather than a continuous trend over time. PIR was calculated in 2-month and 2-week time ranges before available HbA1c measurement. One-hundred ninety-seven patients with T1D and 36 with T2D were recruited. HbA1c and PIR were inversely associated (2 months: R -0.72, 2 weeks R -0.70; p < 0.0001) in all subjects. The relationship did not change when T1D and T2D patients were analyzed separately. For every 10% change of PIR, there was a change of HbA1c by 0.4%. CONCLUSIONS: Our study, for the first time, demonstrates a significant correlation between HbA1c and PIR calculated by DMS. DMS offers additional information useful in disease management of patients with T1D and T2D performing SMBG.

Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study.

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect.

Transaminase levels in the upper normal range are associated with oral hypoglycemic drug therapy failure in patients with type 2 diabetes.

Incident diabetes and the worsening of diabetes have recently been linked to hepatic steatosis. Aim of our study was to determine whether oral hypoglycemic agent failure is associated with higher transaminase levels (valid measure of liver steatosis). We selected 200 patients, attenders (3 consecutive annual evaluations) in our clinic, with type 2 diabetes among which 100 with oral hypoglycemic agents failure and 100 who were still responsive to oral therapy. Failure to therapy was defined as glycated hemoglobin >7.5% despite maximal-dose oral therapy. We analyzed patient histories and laboratory data. Compared with oral-therapy-responsive patients, those with failure had a significantly higher level mostly of alanine aminotransferase at the time of therapy failure and 2 years before. They were more likely to have had symptoms of hyperglycemia at the time of diabetes diagnosis. Regression analysis indicated that each 5-unit increase in transaminase levels independently increased the risk for oral hypoglycemic agents failure by 1.70. Higher liver transaminase levels, especially in patients who had symptomatic hyperglycemia at diabetes diagnosis, associate with oral hypoglycemic agent failure. The possible pathogenetic link between transaminase and declining islet function might consist of insulin resistance and increased circulating fatty acid levels, in turn causing liver steatosis and beta-cell dysfunction.

Exenatide improves glycemic variability assessed by continuous glucose monitoring in subjects with type 2 diabetes.

BACKGROUND: Daily glycemic fluctuation leads to development of long-term complications. The aim of our pilot study was to determine if exenatide reduces glycemic variability, assessed with a continuous glucose monitoring (CGM) system, compared with glimepiride. METHODS: We enrolled six consecutive subjects with type 2 diabetes, for whom exenatide was suggested as second-line treatment, and six control subjects, for whom glimepiride was suggested as second-line treatment. CGM was performed at baseline and after 16 weeks of treatment. As measures of glycemic variability we calculated the total daily mean glucose (MG), SD, and mean amplitude of glycemic excursions (MAGE). RESULTS: Exenatide significantly reduced MG, SD, and MAGE, whereas glimepiride did not. Fasting glucose and glycated hemoglobin were lowered in both groups, even if the reduction was not significant. CONCLUSION: Exenatide can reduce glycemic variability compared with glimepiride, providing additional beneficial effects in controlling glucose homeostasis.