Lower Frequency Of Hypoglycemia Research Articles

Sugar and stops in drivers with insulin-dependent type 1 diabetes

BackgroundDiabetes is a major public health challenge, affecting millions of people worldwide. Abnormal physiology in diabetes, particularly hypoglycemia, can cause driver impairments that affect safe driving. While diabetes driver safety has been previously researched, few studies link real-time physiologic changes in drivers with diabetes to objective real-world driver safety, particularly at high-risk areas like intersections. To address this, we investigated the role of acute physiologic changes in drivers with type 1 diabetes mellitus (T1DM) on safe stopping at stop intersections. Methods18 T1DM drivers (21–52 years, μ = 31.2 years) and 14 controls (21–55 years, μ = 33.4 years) participated in a 4-week naturalistic driving study. At induction, each participant’s personal vehicle was instrumented with a camera and sensor system to collect driving data (e.g., GPS, video, speed). Video was processed with computer vision algorithms detecting traffic elements (e.g., traffic signals, stop signs). Stop intersections were geolocated with clustering methods, state intersection databases, and manual review. Videos showing driver stop intersection approaches were extracted and manually reviewed to classify stopping behavior (full, rolling, and no stop) and intersection traffic characteristics. ResultsMixed-effects logistic regression models determined how diabetes driver stopping safety (safe vs. unsafe stop) was affected by 1) disease and 2) at-risk, acute physiology (hypo- and hyperglycemia). Diabetes drivers who were acutely hyperglycemic (≥ 300 mg/dL) had 2.37 increased odds of unsafe stopping (95% CI: 1.26–4.47, p = 0.008) compared to those with normal physiology. Acute hypoglycemia did not associate with unsafe stopping (p = 0.537), however the lower frequency of hypoglycemia (vs. hyperglycemia) warrants a larger sample of drivers to investigate this effect. Critically, presence of diabetes alone did not associate with unsafe stopping, underscoring the need to evaluate driver physiology in licensing guidelines. ConclusionThis study links acute, abnormal physiologic fluctuations in drivers with diabetes to driver safety based on unsafe stopping at stop-controlled intersections, providing recommendations for clinicians aimed at improving patient safety, fair licensing guidelines, and targets for developing advanced driver assistance systems.

Exenatide and Renal Outcomes in Patients with Type 2 Diabetes and Diabetic Kidney Disease

Background: Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD). Methods: We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) >0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes. Results: Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m². After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (p = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, p = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group. Conclusion: Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.

26-LB: Exenatide and Renal Outcomes in Patients with Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter, Randomized, Parallel Study

Aim: This trial aimed to assess the effects of exenatide, a GLP-1RA, on renal outcomes in patients with T2DM and DKD. Methods: We performed a randomized, parallel study conducted in 4 general hospitals. T2DM patients with an eGFR≥30mL/min/1.73m2 and macroalbuminuria, defined as 24h-urinary albumin-creatinine ratio (UAER) >0.3g/24h, were randomized 1:1 to receive exenatide twice daily plus glargine or lispro insulin plus glargine for 24 weeks. The primary outcome was percentage change in 24h-UAER after 24 weeks of intervention comparing to baseline measurement. The secondary outcomes included the percentage change in urinary ACR, change in 24h-UAER, ACR, HbA1c, FPG, body weight and blood pressure. The safety outcomes include rates of hypoglycemia, adverse events and change in eGFR during the follow up. Results: Between March 2016 and April 2019, 92 patients were randomized and took at least one dose of study drug. The mean age of the participants was 56 years. At baseline, the median 24h-UAER was 1512.0 mg/24h (IQR 782.5-2818.0), and mean eGFR was 70.4 mL/min/1.73 m2 (SD 23.4). After 24 weeks, exenatide reduced the percentage change of the 24h-UAER (difference between groups was 29.7%, p=0.0255), the percentage change of ACR (difference between groups was 28.4%, p=0.0395) and the absolute change of ACR (difference between groups was 607.8 mg/g, p=0.0209) but had no significant difference on the absolute change of 24h-UAER than the control group. Meanwhile, the body weight declined by 1.3kg with exenatide (difference between groups was 2.7kg, p=0.0001). There was no difference between two groups on the change in HbA1c, FPG, blood pressure or eGFR. Comparing to the control group, lower frequency of hypoglycemia as well as more gastrointestinal adverse events were in intervention group. Conclusions: Exenatide twice daily plus glargine for 24 weeks resulted in significant reduction of albuminuria in T2DM patients with DKD. Disclosure X. Wang: None. Q. Zhang: None. M. Guan: None. S. Sheng: None. W. Mo: None. M. Zou: None. J. Li: None. J. Bi: None. X. Tang: None. J. He: None. G. Xu: None. P. Li: None. H. Zhang: None. Y. Xue: None.

966-P: The Long-Term Impact of a Flash Glucose Monitoring System on Glycemic Control

Background: Tight control of blood glucose with lower frequency of hypoglycemia is required to prevent diabetic complications. However, HbA1c doesn’t reflect intraday- and interday glycemic excursions. The aim of this study is to characterize fluctuations in blood glucose levels with the flash glucose monitoring (FGM) and to observe the course of patients in whom this information was used to direct their daily medical treatment. Methods: This 52-week, retrospective observational study involved diabetic patients who wore the FGM device (FreeStyle Libre Pro®) for 2 weeks. Changes in HbA1c were observed by clinical phenotypes of diabetes and manifestations of glucose variability. The frequency of hypoglycemia was analyzed in patients who had performed SMBG. We divided patients into two groups (those who received a check-up after 1 week or 2 weeks after starting to wear the device) and compared their change in of HbA1c. The differences of HbA1c change from baseline were analyzed by the t-test and P-values < 0.05 were considered significant. Results: Of 114 patients who received a FGM device, 79 were enrolled in the study (type 1: n=14, type 2: n=62, other: n=3). Overall, the mean HbA1c (%) was significantly decreased at week 12 compared with baseline (8.35 vs. 7.61, P<0.001) and this reduction was continued at week 24 (7.78, P<0.001) and week 52 (7.62, P<0.001). Only nutritional guidance with FGM-use was associated with a similar reduction in HbA1c at week 52 compared with medication regimen changes (0.77 vs. 0.68, P=0.37). The frequency of hypoglycemia was lower at week 12, 24, and 52 compared with baseline. A trend towards a greater reduction in HbA1c at week 12 was observed in patients who received a check-up 1 week after initiating to wear FGM device comparted with those with a check-up 2 weeks afterwards (0.94 vs. 0.72, p=0.14). Conclusion: Visualization of glucose variability with a FGM device was safe and has the potential to improve glucose profiles for a long term even though this method was only a temporary measure. Disclosure A. Fujiya: None. T. Kiyose: None. T. Shibata: None. H. Sobajima: None.

Glycemic Variability and Insulin Needs in Patients with Type 1 Diabetes Mellitus Supplemented with Vitamin D: A Pilot Study Using Continuous Glucose Monitoring System.

Recent studies suggest that glycemic variability could influence the risk of complications in Type 1 Diabetes Mellitus (T1DM). There are no data about the action of Vitamin D (VD) on glycemic variability. Our pilot study aims to evaluate glycemic variability and insulin needs in patients with T1DM supplemented with VD. 22 Patients received doses of 4000 and 10000 IU/day of cholecalciferol for 12 weeks, according to the patient's baseline VD levels and underwent continuous glucose monitoring system. Correlations were found between percentage variation (Δ) of glycemia standard deviation (ΔSDG), calculated using continuous glucose monitoring, with Δ of basal (r = 0.6; p <0.01) and total insulin dose (r = 0.6; p <0.01). Correlations between VD status after supplementation and Δ of prandial (r = 0.5; p <0.05) and total insulin dose (r = 0.4; p <0.05) were found, suggesting that the dose of insulin needed by patients is lower when VD status is better. We divided patients in two subgroups: SDG improved (subgroup 1; N = 12 (55%)) and SDG worsened (subgroup 2; N = 10 (45%)). Group 1, compared to subgroup 2, required a lower insulin dose (Δbasal insulin dose = -8.0 vs. 6.3%; p <0.05) and had a lower frequency of hypoglycemia (27% vs. 64%, hypoglycemias/days evaluated; p <0.01). Our study suggests a relation between VD supplementation, improved glycemic variability, lower insulin needs and lower frequency of hypoglycemia in patients with T1DM.

Initial combination therapy for patients with type 2 diabetes mellitus: considerations for metformin plus linagliptin

SummaryFor patients with type 2 diabetes mellitus, management of hyperglycemia is typically complex, and few patients successfully achieve and maintain recommended targets for glycated hemoglobin (HbA1c). Increasingly, combination therapy is recommended early in the disease course, or even directly at diagnosis in patients with relatively high HbA1c levels. A recent randomized, placebo-controlled, Phase III trial investigated the initial combination of linagliptin and metformin in patients with inadequate glycemic control to assess the benefits of initial combination compared with monotherapy. Linagliptin and metformin act in complementary ways, and the combination treatment showed superior efficacy compared with either monotherapy. Notably, responses were largest in patients with higher baseline HbA1c levels compared with moderate levels, suggesting this combination could be considered in these patients. This may be particularly relevant for those unwilling to start insulin because they prefer oral therapy or need to avoid body weight gain. Neither metformin nor linagliptin is associated with weight gain, and in this trial the combination was also weight neutral. As this combination therapy was well tolerated, with a low frequency of hypoglycemia, these findings suggest that initial combination of linagliptin plus metformin may have advantages for a large proportion of patients in clinical practice.

Achievement of Target A1C Levels With Negligible Hypoglycemia and Low Glucose Variability in Youth With Short-Term Type 1 Diabetes and Residual β-Cell Function

OBJECTIVETo determine exposure to hyper- and hypoglycemia using blinded continuous glucose monitoring (CGM) profiles in youth with type 1 diabetes (T1D) with residual β-cell function during the first year of insulin treatment.RESEARCH DESIGN AND METHODSBlinded, 3–7 day CGM profiles were obtained in 16 short-term T1D patients (age 8–18 years, T1D duration 6–52 weeks) who had peak C-peptide levels ranging from 0.46 to 1.96 nmol/L during a mixed-meal tolerance test. Results in this short-term group were compared with those in 34 patients with well-controlled, longer-term T1D (duration ≥5 years), matched for age and A1C with the short-term T1D group, and with those in 26 age-matched nondiabetic individuals.RESULTSDespite matching for A1C, and therefore similar mean sensor glucose levels in the two T1D groups, short-term T1D participants had a lower frequency of hypoglycemia (0.3 vs. 7.6%, P < 0.001), a trend toward less hyperglycemia (17 vs. 32%, P = 0.15), and a greater percentage in the target range (median 77 vs. 60%, P = 0.02). Indeed, the percentage of sensor glucose levels ≤70 mg/dL in the short-term T1D group (0.3%) did not differ from those in the nondiabetic group (1.7%, P = 0.73). The coefficient of variation of sensor glucose levels (an index of glucose variability) was lower in short-term vs. longer-term T1D participants (27 vs. 42%, respectively, P < 0.001).CONCLUSIONSIn youth with short-term T1D who retain residual β-cell function, there is negligible exposure to hypoglycemia and lower glucose variability than in youth with well-controlled T1D of longer duration.

Types of Diabetes that the Dipeptidyl Peptidase-4 Inhibitor May Act Effectively and Safely

Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent the inactivation of glucagon-like peptide-1 (GLP-1). This protein, released from the gut following ingestion of a meal, stimulates insulin secretion and inhibits glucagon secretion. Compared with other anti-diabetic drugs, the pharmacological characteristics of DDP-4 inhibitor include improvement in postprandial hyperglycemia, low frequency of hypoglycemia, prevention of development of obesity, few adverse events. Taking account of pharmacological characteristic and our therapeutic experiences with DPP-4 inhibitor, we believe that DPP-4 inhibitor may be a useful and safe oral anti-diabetic drug for diabetes in the elderly people, diabetes complicated with obesity, chronic hepatitis/liver cirrhosis, and steroid-induced diabetes.

Sitagliptin: A novel agent for the management of type 2 diabetes mellitus

The pharmacologic, pharmacokinetic, safety, clinical efficacy, and role of sitagliptin in the management of type 2 diabetes mellitus are reviewed. Sitagliptin is a dipeptidyl-peptidase IV (DPP4) inhibitor that increases insulin release and decreases glucagon levels by preventing the activation of incretin hormones--glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. The clinical trials reviewed provide evidence that sitagliptin, either alone or in combination with metformin or thiazolidinediones, is effective in reducing glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and two-hour postprandial glucose levels in patients with type 2 diabetes. Specifically, sitagliptin has a role in patients who have been compliant with their oral hypoglycemic agents but unable to attain target HbA(1c) values with monotherapy and lifestyle modifications. Sitagliptin is generally well tolerated, with the frequency of adverse events being similar to placebo and a low frequency of hypoglycemia. Sitagliptin does not appear to alter the pharmacokinetics of metformin, rosiglitazone, glyburide, simvastatin, warfarin, or oral contraceptives. The addition of sitagliptin to a patient's oral antidiabetic regimen would necessitate close monitoring for adverse events and possible drug interactions. The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione. No formal pharmacoeconomic evaluations of sitagliptin therapy have been conducted. Sitagliptin, a DPP4 inhibitor, offers a novel treatment option for patients with type 2 diabetes mellitus.