The Association Between Ambient Temperature and Hypoglycemia in People Living With Type 1 Diabetes: A Case Time Series Analysis Using Real-Time Continuous Glucose Monitoring.

Self-monitoring of blood glucose is essential to optimise glycaemic control in type 1 diabetes mellitus. Continuous glucose monitoring (CGM) systems measure interstitial fluid glucose levels to provide semi-continuous information about glucose levels, which identifies fluctuations that would not have been identified with conventional self-monitoring. Two types of CGM systems can be defined: retrospective systems and real-time systems. Real-time systems continuously provide the actual glucose concentration on a display. Currently, the use of CGM is not common practice and its reimbursement status is a point of debate in many countries. To assess the effects of CGM systems compared to conventional self-monitoring of blood glucose (SMBG) in patients with diabetes mellitus type 1. We searched The Cochrane Library, MEDLINE, EMBASE and CINAHL for the identification of studies. Last search date was June 8, 2011. Randomised controlled trials (RCTs) comparing retrospective or real-time CGM with conventional self-monitoring of blood glucose levels or with another type of CGM system in patients with type 1 diabetes mellitus. Primary outcomes were glycaemic control, e.g. level of glycosylated haemoglobin A1c (HbA1c) and health-related quality of life. Secondary outcomes were adverse events and complications, CGM derived glycaemic control, death and costs. Two authors independently selected the studies, assessed the risk of bias and performed data-extraction. Although there was clinical and methodological heterogeneity between studies an exploratory meta-analysis was performed on those outcomes the authors felt could be pooled without losing clinical merit. The search identified 1366 references. Twenty-two RCTs meeting the inclusion criteria of this review were identified. The results of the meta-analyses (across all age groups) indicate benefit of CGM for patients starting on CGM sensor augmented insulin pump therapy compared to patients using multiple daily injections of insulin (MDI) and standard monitoring blood glucose (SMBG). After six months there was a significant larger decline in HbA1c level for real-time CGM users starting insulin pump therapy compared to patients using MDI and SMBG (mean difference (MD) in change in HbA1c level -0.7%, 95% confidence interval (CI) -0.8% to -0.5%, 2 RCTs, 562 patients, I(2)=84%). The risk of hypoglycaemia was increased for CGM users, but CIs were wide and included unity (4/43 versus 1/35; RR 3.26, 95% CI 0.38 to 27.82 and 21/247 versus 17/248; RR 1.24, 95% CI 0.67 to 2.29). One study reported the occurrence of ketoacidosis from baseline to six months; there was however only one event. Both RCTs were in patients with poorly controlled diabetes.For patients starting with CGM only, the average decline in HbA1c level six months after baseline was also statistically significantly larger for CGM users compared to SMBG users, but much smaller than for patients starting using an insulin pump and CGM at the same time (MD change in HbA1c level -0.2%, 95% CI -0.4% to -0.1%, 6 RCTs, 963 patients, I(2)=55%). On average, there was no significant difference in risk of severe hypoglycaemia or ketoacidosis between CGM and SMBG users. The confidence interval however, was wide and included a decreased as well as an increased risk for CGM users compared to the control group (severe hypoglycaemia: 36/411 versus 33/407; RR 1.02, 95% CI 0.65 to 1.62, 4 RCTs, I(2)=0% and ketoacidosis: 8/411 versus 8/407; RR 0.94, 95% CI 0.36 to 2.40, 4 RCTs, I(2)=0%).Health-related quality of life was reported in five of the 22 studies. In none of these studies a significant difference between CGM and SMBG was found. Diabetes complications, death and costs were not measured.There were no studies in pregnant women with diabetes type 1 and in patients with hypoglycaemia unawareness. There is limited evidence for the effectiveness of real-time continuous glucose monitoring (CGM) use in children, adults and patients with poorly controlled diabetes. The largest improvements in glycaemic control were seen for sensor-augmented insulin pump therapy in patients with poorly controlled diabetes who had not used an insulin pump before. The risk of severe hypoglycaemia or ketoacidosis was not significantly increased for CGM users, but as these events occurred infrequent these results have to be interpreted cautiously.There are indications that higher compliance of wearing the CGM device improves glycosylated haemoglobin A1c level (HbA1c) to a larger extent.

Objective To evaluate the value of real time continuous blood glucose monitoring system (RT-CGMS) versus intermittent blood glucose monitoring (IGM) in the critically ill patients under intensive insulin therapy (IIT) . Methods A systematic searching randomized and controlled trials (RCT) in databases was performed for meta-analysis by Review Manager 5.2 software. Outcomes were hypoglycemia episode, alteration of mean blood glucose level, the percentage of time at a blood glucose level within optimal target range, and the early mortalities. Results Six studies, totally 531 patients, were included in this meta-analysis. The pooled SMD of mean blood glucose level was =-0.21 (95% SMD: -0.43 - 0.01, P =0.07) . The pooled SMD of percentage of time at a blood glucose level within optimal target range was 0.20 (95% SMD: -0.09 -0.49, P =0.18) . The pooled OR of hypoglycemia episode frequency was 0.20 (95% CI: 0.09 -0.43, P <0.01) . The pooled OR of early mortalities was 0.35 (95% CI: 0.14 -0.89, P =0.03) . Conclusions In critically ill patients under the intensive insulin therapy, RT-CGMS had obvious beneficial effect on reducing hypoglycemic events. RT-CGMS had no obvious beneficial effect on keeping blood glucose level within optimal target range. Key words: Critically ill patients; Real time continuous glucose monitoring system; Intensive insulin therapy; Meta-analysis

To evaluate the influence of extreme ambient temperature on mortality and years of life lost (YLL) in Chongqing. The daily mortality, meteorology and air pollution index data in Chongqing from the 1(st) January 2010 to the 31(st) December 2013 were collected. Distributed lag non-linear model (DLNM) was used to assess the influence of daily ambient temperature on daily number of deaths and daily YLL respectively. The delayed and cumulative effects of extreme temperature on sex, age, and cause-specific mortality were also assessed. The relationships between ambient temperature and non-accidental, cardiovascular disease and respiratory disease mortalities and YLL were U-shaped or W-shaped. The effect of heat was obvious on that day, peaked on day 7, and lasted for two weeks, whereas the effect of cold was obvious a week later and lasted for a month. As 1 ℃ increase of ambient temperature, the cumulative relative risks (CRR) of high temperature across lag 0-7 days on non-accidental, respiratory disease and cardiovascular disease mortalities were 1.05 (95%CI: 1.03-1.07), 1.08 (95%CI: 1.05-1.11) and 1.05 (95%CI: 1.01-1.09) respectively. The effects of heat on YLL for each cause were 23.81 (95%CI: 12.31-35.31), 14.34 (95%CI: 8.98-19.70) and 4.43 (95%CI: 1.64-7.21), respectively. On cold days, 1 ℃ decrease of ambient temperature was correlated with an increase in CRR of 1.06 (95%CI: 1.04-1.08), 1.09 (95%CI:1.06-1.12) and 1.06 (95%CI: 1.02-1.11) from lag 0 to 14 for non-accidental, respiratory disease and cardiovascular disease mortalities, respectively. The estimated YLL were 23.34 (95%CI: 10.04-36.64), 16.39 (95%CI: 10.19-22.59) and 2.61 (95%CI: -0.61-5.82). People aged ≥65 years tend to have higher CRR and YLL than those aged <65 years. On high temperature days, the CRR in women was higher than that in men, while the YLL in women was lower than that in men. On low temperature days, both the CRR and YLL in women were higher than those in men. Both high and low ambient temperature have adverse health effects. People aged ≥65 years are more sensitive to both high and low ambient temperature. Younger men are more sensitive to high ambient temperature and women and elder men are sensitive to low ambient temperature. It is necessary to take targeted measures to protect the population in Chongqing from the adverse influence of extreme ambient temperature.

Bunching behaviour in housed dairy cows at higher ambient temperatures

A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with

The impressive progress achieved in recent years in diabetes technologies has made diabetes technological devices such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) a significant part of diabetes treatment. Many studies conducted in recent years emphasized the advantages of using these technologies. The concept of the “human factor” in diabetes technologies as discussed in this chapter has several different aspects. First, it can refer to the way patients are satisfied with the use of the device and whether it is perceived convenient or inconvenient. For example, is the device perceived as “user friendly” (easy to learn and to operate, comfortable, does not cause many hassles). Second, there is the issue of effectiveness of the technology as it relates to their day-to-day diabetes management. For example, there is an improvement in glycemic control when one diabetes treatment regimen is compared to another (i.e., CSII vs. multiple daily injections (MDI)). Those two fundamental aspects may have different meanings for different groups. For example, different age groups (toddlers, children, adolescents, young adults, adults, and older people) can see different advantages and disadvantages in technological devices. The feasibility and utility of technological devices also need to fit the environments in which they will be used, such as school, the work place, and/or home. Specific subgroups such as diabetic youth with eating disorders can have unique interactions with diabetes technologies. In addition, diabetes technologies can be used as a measurement device, providing more rich and accurate data about patients' self-care that can contribute to our understanding of concepts such as adherence and satisfaction, and they can provide measurement tools to assess how glycemic control can effect cognition and intelligence. The present chapter will review articles published in the last year that have studied some of these issues.

The effect of short-term use of the Guardian RT continuous glucose monitoring system on fear of hypoglycaemia in patients with type 1 diabetes mellitus

Background: The I HART CGM study showed that real-time continuous glucose monitoring (RT-CGM) has greater beneficial impact on hypoglycemia than intermittent flash glucose monitoring (flash) in adults with type 1 diabetes (T1D) at high risk. The impact of continuing RT-CGM or switching from flash to RT-CGM for another 8 weeks was then evaluated.Methods: Prospective randomized parallel group study with an extension phase. After a 2-week run-in with blinded CGM, participants were randomized to either RT-CGM or flash for 8 weeks. All participants were then given the option to continue with RT-CGM for another 8 weeks. Glycemic outcomes at 8 weeks are compared with the 16-week endpoint.Results: Forty adults with T1D on intensified multiple daily insulin injections and with impaired awareness of hypoglycemia or a recent episode of severe hypoglycemia were included (40% female, median [IQR] age 49.5 [37.5–63.5] years, diabetes duration 30.0 [21.0–36.5] years, HbA1c 56 [48–63] mmol/mol, and Gold Score 5 [4–5]), of whom 36 completed the final 16-week extension. There was a significant reduction in percentage time in hypoglycemia (<3.0 mmol/L) in the group switching from flash to RT-CGM (from 5.0 [3.7–8.6]% to 0.8 [0.4–1.9]%, P = 0.0001), whereas no change was observed in the RT-CGM group continuing with the additional 8 weeks of RT-CGM (1.3 [0.4–2.8] vs. 1.3 [0.8–2.5], P = 0.82). Time in target (3.9–10 mmol/L) increased in the flash group after switching to RT-CGM (60.0 [54.5–67.8] vs. 67.4 [56.3–72.4], P = 0.02) and remained the same in the RT-CGM group that continued with RT-CGM (65.9 [54.1–74.8] vs. 64.9 [49.2–73.9], P = 0.64).Conclusions: Our data suggest that switching from flash to RT-CGM has a significant beneficial impact on hypoglycemia outcomes and that continued use of RT-CGM maintains hypoglycemia risk benefit in this high-risk population.

Real-time continuous glucose monitoring (RT-CGM) improves hemoglobin A1c (A1C) and hypoglycemia in people with type 1 diabetes mellitus and those with type 2 diabetes mellitus (T2DM) on prandial insulin; however, it has not been tested in people with T2DM not taking prandial insulin. We evaluated the utility of RT-CGM in people with T2DM on a variety of treatment modalities except prandial insulin. We conducted a prospective, 52-week, two-arm, randomized trial comparing RT-CGM (n = 50) versus self-monitoring of blood glucose (SMBG) (n = 50) in people with T2DM not taking prandial insulin. Real-time continuous glucose monitoring was used for four 2-week cycles (2 weeks on/1 week off). All patients were managed by their usual provider. This article reports on changes in A1C 0-12 weeks. Mean (± standard deviation) decline in A1C at 12 weeks was 1.0% (± 1.1%) in the RT-CGM group and 0.5% (± 0.8%) in the SMBG group (p = .006). There were no group differences in the net change in number or dosage of hypoglycemic medications. Those who used the RT-CGM for ≥ 48 days (per protocol) reduced their A1C by 1.2% (± 1.1%) versus 0.6% (± 1.1%) in those who used it <48 days (p = .003). Multiple regression analyses statistically adjusting for baseline A1C, an indicator for usage, and known confounders confirmed the observed differences between treatment groups were robust (p = .009). There was no improvement in weight or blood pressure. Real-time continuous glucose monitoring significantly improves A1C compared with SMBG in patients with T2DM not taking prandial insulin. This technology might benefit a wider population of people with diabetes than previously thought.

ObjectivePresent clinicians with an updated overview of empagliflozin for the treatment of type 2 diabetes mellitus (T2DM), with focus on its use in combination regimens. MethodsUsing the Medline database, keyword searches were undertaken to identify literature reporting the use of empagliflozin treatment in clinical trials with a minimum duration of 12 weeks relating to patients with T2DM.

Background: Chronic kidney disease (CKD) is a growing global health problem due to the increasing prevalence of Type 2 Diabetes Mellitus (T2DM). Consequently, the management of T2DM becomes challenging with advancing non-dialysis CKD (n-CKD). Prior studies have not confirmed the accuracy of markers such as serum fructosamine (SF) and glycosylated hemoglobin A1c (HbA1c) in this population. Also, there is a paucity of data on the incidence of hypoglycemia in these patients. The present study is twofold; evaluating the accuracy of HbA1c and exploring the frequency and severity of hypoglycemia in T2DM patients with n-CKD by continuous glucose monitoring (CGM). Methods: We studied 80 patients with T2DM and n-CKD defined as eGFR 0-45 ml/min. Patients wore the CGM (Abbott FreeStyle Libre Pro) for up to 14 days, with glucose recorded every 15 minutes, with a maximum of 1,344 glucose measurements. Blood tests were performed in the fasting state at the end of the 14 day CGM. HbA1C and SF were compared by linear regression to patients’ average glucose concentration (AGC) calculated as all of a patient’s CGM glucose results divided by the total number of measurements. Hypoglycemia was defined as plasma glucose below 70 mg/dL. Results: 80 patients wore the CGM for a mean of 12.6±2.8 days. Mean age was 71.3±10.9 years, 77% of patients were men, 12% were black, and mean eGFR 27.0±11.1 ml/min. The mean glucose concentration was 151.4±55.7 mg/dL, mean HbA1C 7.2±1.5% and SF 304.1±57.2 μmol/L. HbA1C significantly correlated with AGC, r=0.82, p<0.0001. The relationship was characterized by the formula, AGC=31.8 x HbA1C - 73.3. There was no significant correlation between serum fructosamine and AGC, r=0.54, p=0.8. 61/80 (76.2%) patients had at least one hypoglycemic episode. The mean number of episodes was 7.4±8.9, with a range of 0-53 episodes. The mean number of minutes of hypoglycemia was 1501±2165. This represents a mean of 7.4±10.1% of total measurement time being hypoglycemic, compared to studies in T2DM without CKD where the number is closer to 1.5%. Conclusion: HbA1C, but not serum fructosamine, was an excellent measure of glycemic control in patients with T2DM and n-CKD. Confirming this with a larger sample size is imperative for disease management. The high burden of hypoglycemia highlights the need to avoid medications that increase risk of hypoglycemia and consider adjusting glycemic targets in this patient population.

Glycemic management in patients with type 2 diabetes mellitus (T2DM) and CKD can become complicated. One factor that may affect treatment is hypoglycemia. Hypoglycemia risk may be increased by several biologic processes in CKD. The objective of this study was to determine the frequency, severity, and risk factors for hypoglycemia in patients with T2DM and CKD. The design was a prospective observational study. A continuous glucose monitor (CGM) was worn by 80 patients for up to 14 days; glucose was measured every 15 minutes. Patients with T2DM and eGFR <45 ml/min were enrolled. Patients on dialysis were excluded. The primary outcome was to assess the frequency of hypoglycemic episodes during the study period. Hypoglycemic episodes were defined as a reduced glucose concentration (<70 mg/dl) lasting ≥15 minutes. Secondary outcomes included assessment of severity of hypoglycemia and risk factors for its development. A total of 80 patients wore the CGM for a mean of 12.7±2.9 days. Hypoglycemic events occurred in 61 of 80 patients (76%) with glucose <70 mg/dl, and 49 of 80 (61%) with glucose <60 mg/dl. Prolonged hypoglycemic events (CGM glucose <54 mg/dl for ≥120 consecutive minutes) occurred in 31 patients (39%) with 118 total events. Most hypoglycemic episodes occurred overnight, from 1:00 am to 9:00 am. By multivariate analysis, lower hemoglobin A1c and treatment with insulin were two modifiable risk factors for hypoglycemic events. Patients with T2DM and CKD have frequent periods of hypoglycemia that can be severe and prolonged. Hemoglobin A1c does not portray the full scope of hypoglycemia risk. This study illustrates the need for careful monitoring of glucose levels in patients with T2DM and CKD.

Real-time continuous glucose monitoring (CGM) has changed the way people with type 1 diabetes mellitus (T1DM) and health care providers perceive diabetes management and glucose control. The purpose of this meta-analysis was to compare the emotional well-being of adults with T1DM who used CGM and those using conventional self-monitoring of blood glucose (SMBG). The MEDLINE/PubMed, Cochrane Library / Embase, CINAHL, Scopus, Web of Science, and ProQuest databases were searched for relevant publications. Primary outcome measures were health-related quality of life, glycemic control, and fear of hypoglycemia. Randomized controlled trials and survey studies focused on the quality of life and fear of hypoglycemia among adult patients using CGM and SMBG were included in the analysis. The meta-analysis included 11 studies involving a total of 1228 patients with T1DM. Analysis of the Worry subscale of the Hypoglycemia Fear Survey indicated a reduction of hypoglycemia fear in CGM users compared with SMBG users (Cohen d = –0.24; 95% CI, –0.41 to –0.07; mean difference, –3.15; 95% CI, –5.48 to –0.82). Outcome analysis of studies including the Diabetes Treatment Satisfaction Questionnaire showed Cohen d of 0.23 (95% CI, –0.18 to 0.63). The overall value of Cohen d equaled –0.24 (95% CI, –0.57 to 0.09), indicating a lack of effect of CGM use on improving HbA1c levels; however, after one of the studies was excluded from calculations, the reduction of HbA1c levels was significantly higher in CGM users (Cohen d = –0.33; 95% CI, –0.66 to 0.00; P = 0.047). This is the first quantitative meta-analysis of studies involving adult patients exclusively with T1DM, providing further evidence for the ability of CGM systems to reduce fear of hypoglycemia and improve quality of life. Continuous glucose monitoring systems have advantage over SMBG in adults with T1DM and improve HbA1c levels.

Exercise is important in the management of type 1 diabetes mellitus (T1DM). Modern diabetes care includes the goal that all youth meet guidelines for regular physical activity. Evidence suggests regular physical activity improves cardiovascular health, lipid profiles, psychosocial wellbeing and, possibly, glycemic control in youth with T1DM. However, exercise is especially problematic for children and adolescents because wide glycemic excursions commonly occur during and after exercise and may increase the risk of severe hypoglycemia. In addition, youth with T1DM have abnormal counterregulatory hormone responses, further increasing the risk of exercise-associated hypoglycemia. Recent studies have demonstrated that this risk is present during, and many hours after exercise, and have tested strategies to prevent exercise-induced hypoglycemia in youth. Despite these recent studies, the fear of hypoglycemia remains a major impediment to achieving target glycemic control in youth, targets that have recently been tightened. Equally, data suggests fear of hypoglycemia is the major impediment to participation in regular daily exercise in T1DM. Recent advances in insulin delivery systems and in real time continuous glucose monitoring have improved care for youth with T1DM, allowing safer participation in exercise programs. The impending development and approval of "closed loop" insulin delivery systems (the artificial pancreas) holds great promise for the safe participation in exercise for all youth with T1DM.

Dual devices allow both continuous subcutaneous insulin infusion (CSII) and real-time (RT) continuous glucose monitoring (CGM). Patients usually start with CSII, adding RT-CGM later (CGM post-CSII). Lack of use of RT-CGM is the main limiting factor of dual device results. Initiating RT-CGM before CSII (CGM pre-CSII) could increase RT-CGM frequency use and further improve glycemic control. In this 26-week pilot study, we randomly assigned, via sealed envelopes, 16 CSII and RT-CGM to naive patients 14 years of age or older with type 1 diabetes mellitus (T1DM) to CGM post-CSII or CGM pre-CSII. The Paradigm® Veo™ (Medtronic Inc., Northridge, CA) was the dual device used in all patients. The primary end point was frequency of use of RT-CGM between both groups at week 26. We detected a significant higher RT-CGM frequency use in the CGM pre-CSII group at week 26 (78.4±10.9% vs. 56.0±40.8%; P=0.01), although we did not detect hemoglobin A1c level differences. In addition, CGM pre-CSII patients presented less time in hypoglycemia (average daily area under curve <70 mg/dL per 24 h, 0.87±1.02 mg/dL/day vs. 3.32±2.19 mg/dL/day; P=0.021), and no severe hypoglycemia events were detected during 26 weeks in this group. CGM pre-CSII is effective in increasing RT-CGM frequency use in T1DM patients. This is accompanied by a significant reduction in time in hypoglycemia.