The Predictive Low Glucose Management System in Prevention of Clinically Significant Hypoglycemia in Type 1 Diabetes. A Preliminary Study Identifying the Most Common Events Leading Up to Hypoglycemia During Insulin Pump Therapy.

BACKGROUND/AIM: Prevention of hypoglycemia remains a major challenge in diabetic management, despite the introduction of modern insulin pumps in daily clinical practice. The Low Glucose Suspend (LGS) and the newer Predictive Low Glucose Management (PLGM) systems incorporated in the Medtronic insulin pumps have shown promising results in prevention of hypoglycemia. Our aim was to evaluate the effect of the 2 systems relative to the frequency of clinically significant hypoglycemia in Type 1 diabetes (T1DM). In addition, we investigated the events preceding clinically significant hypoglycemia episodes. METHODS: A cross-sectional study was conducted in 30 T1DM patients using the MiniMed 640G vs. 30 using the MiniMed Veo sensor-augmented insulin pump. All data was recorded during patients' normal daily activity and living conditions. The patients were matched for age and duration of diabetes. RESULTS: PLGM use was associated with lower incidence of clinically significant hypoglycemia (1.9±1.4 vs. 3.6±1.9 episodes per week), along with reduced exposure to hypoglycemia. The data indicated that both pump systems are effective in preventing severe hypoglycemic episodes. In both groups the most common events preceding hypoglycemic episodes included adjustment of hyperglycemia, basal rate increase and miscalculation of carbohydrates. CONCLUSIONS: The results indicated that the use of the Minimed 640G pump system can help reduce the frequency of clinically significant hypoglycemia. Management of hyperglycemia must be addressed in diabetes education programs in order to encourage proper adjustment of high blood glucose levels. Future studies would be useful in exploring the details of the events preceding hypoglycemia episodes in insulin pump users.

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study.

BACKGROUND: In Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM. METHODS: In this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated. RESULTS: GDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ±â€¯1.7) relative to the IVF (37.9 ±â€¯0.9, p < 0.001) and the SC group (38.1 ±â€¯0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007). CONCLUSION: GDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.

Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events.

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; P=0.809). Conclusions Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.

Improvement of metabolic control after 3-month use of real-time continuous glucose monitoring in patients with type 1 diabetes: a multicenter study in Greece.

PURPOSE: To assess the efficacy of a real-time continuous glucose monitoring (RT-CGM) system added to insulin pump therapy for 3 months, in sub-optimally controlled adults with type 1 diabetes mellitus (T1D). METHODS: This was a prospective, multicenter, non-randomized, post-market release study. A total of 43 adult patients with T1D on insulin pump therapy and inadequate glycemic control (HbA1c > 7.0%) participated in the study. The primary endpoint was the change from baseline HbA1c levels. Secondary objectives were to evaluate the impact of the RT-CGM system on glucose variability, daily insulin requirements, and the frequency of hypoglycemic and ketoacidosis events. RESULTS: At 3 months, the baseline HbA1c values decreased from 8.0 (7.6, 8.7) to 7.1 (6.7, 8.0) % (p < 0.001). Nineteen participants (44.2%) had a posttreatment HbA1c level ≤ 7%. Average total daily insulin requirements, as well as the average number of insulin boluses per day, increased significantly after the use of the RT-CGM system. The number of hypoglycemic events recorded did not differ between the first week and last week of RT-CGM usage, while no severe hypoglycemic episodes, ketoacidosis events, or hospitalizations related to diabetes occurred during the 3-month follow-up period. CONCLUSION: Addition of a RT-CGM system to insulin pump therapy for 3 months in inadequately controlled patients with T1D resulted in improved HbA1c levels, without increasing the risk of hypoglycemic events.

Effect of atorvastatin on baroreflex sensitivity in subjects with type 2 diabetes and dyslipidaemia.

In this prospective study, we examined the effect of atorvastatin treatment on baroreflex sensitivity (BRS) in subjects with type 2 diabetes. A total of 79 patients with type 2 diabetes with dyslipidaemia were recruited. A total of 46 subjects were enrolled to atorvastatin 10 mg daily and low-fat diet and 33 patients to low-fat diet only. BRS was assessed non-invasively using the sequence method at baseline, 3, 6 and 12 months. Treatment with atorvastatin increased BRS after 12 months (from 6.46 ± 2.79 ms/mmHg to 8.05 ± 4.28 ms/mmHg, p = 0.03), while no effect was seen with low-fat diet. Further sub-analysis according to obesity status showed that BRS increased significantly only in the non-obese group (p = 0.036). A low dose of atorvastatin increased BRS in non-obese subjects with type 2 diabetes and dyslipidaemia after 1-year treatment. This finding emphasizes the beneficial effect of atorvastatin on cardiovascular system, beyond the lipid-lowering effects.

Incretin-based therapies for type 2 diabetes mellitus: effects on insulin resistance.

Insulin resistance has been associated with the development of type 2 diabetes, obesity, hypertension, dyslipidemia, atherosclerosis, and thus with increased cardiovascular morbidity and mortality. Insulin resistance precedes the onset of type 2 diabetes by many years. Targeting the pathophysiologic defects that characterize the onset of diabetes is more likely to achieve a durable glucose control and to delay disease progression. Incretins are gut-derived peptides that stimulate in a glucose-dependent mechanism insulin secretion and action. Glucose-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors both decrease fasting and postprandial glucose levels. In addition, GLP-1 analogues promote weight loss and exert a favorable effect on several cardiovascular risk factors. Data from human and experimental studies implicate that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin sensitivity. This review summarizes the current knowledge regarding the impact of GLP-1 analogues and DPP-4 inhibitors on insulin resistance.

Improved glycemic control through continuous glucose sensor-augmented insulin pump therapy: prospective results from a community and academic practice patient registry.

BACKGROUND: Conducted by highly experienced investigators with abundant time and resources, phase III studies of continuous glucose sensing (CGS) may lack generalizability to everyday clinical practice. METHOD: Community or academic practices in six Central and Eastern European or Mediterranean countries prospectively established an anonymized registry of consecutive patients with type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump therapy with the Paradigm X22 (Medtronic MiniMed, Northridge, CA) under everyday conditions, without prior CGS with another device. We compared glycosylated hemoglobin (GHb) values before and after 3 months of CGS and assessed relationships between insulin therapy variables and glycemia-related variables at weeks 1, 4, and 12 of CGS. RESULTS: Of 102 enrolled patients, 85 (83%) with complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were evaluable. Evaluable patients were approximately 54% male and approximately 75% adult (mean age, 33.2 +/- 16.9 years) with longstanding diabetes and high personal/family education levels. Mean GHb declined significantly after 3 months of CGS (7.55 +/- 1.33% at baseline to 6.81 +/- 1.08% after 12 weeks, 0.74% absolute decrease, P < 0.001). The absolute GHb reduction correlated significantly (P < 0.0005) with baseline GHb: larger absolute reductions tended to occur when baseline levels were higher. An increased basal insulin dose as a percentage of the total daily insulin dose and a decreased daily bolus count from week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12. CONCLUSIONS: CGS-augmented insulin pump therapy appears to improve glycemic control in type 1 diabetes in varied everyday practice settings.