-
1.
Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial.
Benhamou, PY, Franc, S, Reznik, Y, Thivolet, C, Schaepelynck, P, Renard, E, Guerci, B, Chaillous, L, Lukas-Croisier, C, Jeandidier, N, et al
The Lancet. Digital health. 2019;(1):e17-e25
Abstract
BACKGROUND Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. METHODS In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. FINDINGS Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING French Innovation Fund, Diabeloop.
-
2.
Mediation of the association of smoking and microvascular complications by glycemic control in type 1 diabetes.
Braffett, BH, Rice, MM, Young, HA, Lachin, JM
PloS one. 2019;(1):e0210367
Abstract
Studies have demonstrated the adverse effects of smoking on the risk of microvascular complications; however, few have also examined the potential mediating effects of glycemic control. Using data from the Diabetes Control and Complications Trial (DCCT 1983-1993), we describe the acute and long-term risks of smoking on glycemic control and microvascular complications in a well-characterized cohort of participants with type 1 diabetes. The DCCT recorded self-reported smoking behaviors, glycemic exposure based on HbA1c, and complications status. Generalized linear mixed models were used to assess whether time-dependent measurements of smoking predict HbA1c levels. Cox proportional hazard models were used to assess time-dependent smoking exposures as predictors of retinopathy and nephropathy. During a mean of 6.5 years of follow-up, current smokers had consistently higher HbA1c values and were at a higher risk of retinopathy and nephropathy compared with former and never smokers. These risk differences were attenuated after adjusting for HbA1c suggesting that the negative association of smoking on glycemic control is partially responsible for the adverse association of smoking on the risk of complications in type 1 diabetes. These findings support the potential for a beneficial effect of smoking cessation on complications in type 1 diabetes.
-
3.
The health effects of medical nutrition therapy by dietitians in patients with diabetes: A systematic review and meta-analysis: Nutrition therapy and diabetes.
Razaz, JM, Rahmani, J, Varkaneh, HK, Thompson, J, Clark, C, Abdulazeem, HM
Primary care diabetes. 2019;(5):399-408
Abstract
AIMS: Intensive lifestyle, dietary interventions and patient education have been recommended as key milestones in to facilitate the management of Diabetes and contain the growing incidence. We performed a systematic review and meta-analysis to assess the health benefits of medical nutrition therapy among patients with diabetes. DESIGN A systematic search was performed in MEDLINE/PubMed, SCOPUS, and Cochrane library from onset up to February 2019 to identify trials investigating the health effect of Medical nutrition (MNT) in patients with diabetes. Random-effects models were used to calculate the effect sizes as weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS Eleven studies containing 1227 participants were included in the meta-analysis. Pooled results showed a significant reduction in Fasting blood sugar (FBS) (WMD= -8.85mg/dl, 95% CI: -14.41, -3.28), HbA1c (WMD: -0.43%, 95% CI: -0.69, -0.17), weight (WMD: -1.54kg, 95% CI: -2.44, -0.64), Body mass index (BMI) (WMD: -0.34 Kg/m2, 95% CI: -0.52, -0.17), waist circumference (WMD: -2.16cm, 95% CI: -4.09, -0.23), cholesterol (WMD: -4.06mg/dl, 95% CI: -7.31, -0.81), Systolic blood pressure (SBP) (WMD: -7.90mmHg, 95% CI: -13.03, -2.77). Results of meta-regression analysis based on age of participants and duration of intervention were not significant. CONCLUSIONS Patients with diabetes who received medical nutrition therapy showed significant improvements in outcome measures of FBS, HbA1c, weight, BMI, waist circumference, cholesterol, and SBP.
-
4.
Is fasting plasma glucose in early pregnancy a better predictor of adverse obstetric outcomes than glycated haemoglobin?
Mañé, L, Flores-Le Roux, JA, Pedro-Botet, J, Gortazar, L, Chillarón, JJ, Llauradó, G, Payà, A, Benaiges, D
European journal of obstetrics, gynecology, and reproductive biology. 2019;:79-84
Abstract
OBJECTIVES To determine, in a multi-ethnic cohort, the suitability of first-trimester fasting plasma glucose and HbA1c levels in non-diabetic range to identify women without diabetes at increased pregnancy risk. STUDY DESIGN A retrospective analysis of a prospective cohort between April 2013 and September 2015. Universal testing for fasting plasma glucose and HbA1c levels at the first antenatal blood sampling was performed and women were screened for gestational diabetes mellitus at 24-28 weeks' gestation. Primary outcomes were macrosomia and pre-eclampsia, and secondary outcomes preterm delivery, Caesarean section and large-for-gestational age. Different fasting plasma glucose and HbA1c cut-off levels were assessed for associations with outcomes. RESULTS 1,228 pregnancies were included for outcome analysis. After adjustment for potential confounders, no association was found between fasting plasma glucose levels and pregnancy outcomes. Women with an HbA1c ≥5.8% (39.9 mmol/mol) showed an increased risk of macrosomia (OR 2.69, 95% CI 1.16-6.24); an HbA1c ≥5.9% (41 mmol/mol) threshold was independently associated with a three-fold risk of pre-eclampsia (95% CI 1.03-9.9) and an HbA1c ≥6.0% (42.1 mmol/mol) with a four-fold risk of large-for-gestational age (95% CI 1.49-11.07). CONCLUSIONS In a multi-ethnic population, first-trimester fasting plasma glucose levels were not a better predictor of pregnancy complications than HbA1c. Further, an early HbA1c ≥5.8% (39.9 mmol/mol) threshold is already associated with an increased risk of macrosomia.
-
5.
Pharmacist-led therapeutic carbohydrate restriction as a treatment strategy for type 2 diabetes: the Pharm-TCR randomized controlled trial protocol.
Durrer, C, McKelvey, S, Singer, J, Batterham, AM, Johnson, JD, Wortman, J, Little, JP
Trials. 2019;(1):781
Abstract
BACKGROUND The current treatment paradigm for type 2 diabetes mellitus (T2D) typically involves use of multiple medications to lower glucose levels in hope of reducing long-term complications. However, such treatment does not necessarily address the underlying pathophysiology of the disease and very few patients achieve partial, complete, or prolonged remission of T2D after diagnosis. The therapeutic potential of nutrition has been highlighted recently based on results of clinical trials reporting remission of T2D with targeted dietary approaches. During the initial phase of such interventions that restrict carbohydrates and/or induce rapid weight loss, hypoglycemia presents a notable risk to patients. We therefore hypothesized that delivering very low-carbohydrate, low-calorie therapeutic nutrition through community pharmacies would be an innovative strategy to facilitate lowering of glycated hemoglobin (A1C) while safely reducing the use of glucose-lowering medications in T2D. METHODS A community-based randomized controlled trial that is pragmatic in nature, following a parallel-group design will be conducted (N = 200). Participants will have an equal chance of being randomized to either a pharmacist-led, therapeutic carbohydrate restricted (Pharm-TCR) diet or guideline-based treatment as usual (TAU). Pharm-TCR involves a 12-week very low carbohydrate, calorie-restricted commercial diet plan led by pharmacists and lifestyle coaches with pharmacists responsible for managing medications in collaboration with the participants' family physicians. Main inclusion criteria are diagnosis of T2D, currently treated with glucose-lowering medications, age 30-75 years, and body mass index ≥ 30. The primary outcome is a binary measure of use of glucose-lowering medication. Secondary outcomes include A1C, anthropometrics and clinical blood markers. DISCUSSION There are inherent risks involved if patients with T2D who take glucose-lowering medications follow very low carbohydrate diets. This randomized controlled trial aims to determine whether engaging community pharmacists is a safe and effective way to deliver therapeutic carbohydrate restriction and reduce/eliminate the need for glucose-lowering medications in people with T2D. TRIAL REGISTRATION ClinicalTrials.gov, NCT03181165. Registered on 8 June 2017.
-
6.
Lifestyle, Glycosylated Hemoglobin A1c, and Survival Among Patients With Stable Ischemic Heart Disease and Diabetes.
Mancini, GBJ, Maron, DJ, Hartigan, PM, Spertus, JA, Kostuk, WJ, Berman, DS, Teo, KK, Weintraub, WS, Boden, WE, ,
Journal of the American College of Cardiology. 2019;(16):2049-2058
Abstract
BACKGROUND The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial. OBJECTIVES The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD. METHODS Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization. RESULTS During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%. CONCLUSIONS In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).
-
7.
SLEep among diabetic patients and their GlycaEmic control (SLEDGE): A pilot observational study.
Raj, JP, Hansdak, SG, Naik, D, Mahendri, NV, Thomas, N
Journal of diabetes. 2019;(2):122-128
Abstract
BACKGROUND Recent cohort studies have proven the association between sleep deprivation and adverse glycemic control (GC). The aim of this study was to assess the prevalence of excessive daytime sleepiness (EDS), a subjective measure of sleep deprivation, among type 2 diabetic mellitus (T2DM) patients and its association with GC. METHODS This cross-sectional study was conducted between July 2015 and June 2016 in five diabetes clinics in the district of Erode, Tamil Nadu, India. An equal number of consenting patients with T2DM was recruited consecutively from each of the centers, and EDS was measured subjectively using the Epworth sleepiness scale (ESS), whereas GC was assessed using HbA1c levels. RESULTS In all, 126 patients were screened and 102 were found eligible for the study. The prevalence of EDS was 17.5% (95% confidence interval 10.13-24.87). The association between ESS scores and HbA1c levels was analyzed using linear regression after adjusting for age, dietary intake, inflammatory markers (erythrocyte sedimentation rate), depression (Patient Health Questionnaire-9 score) and stress (Perceived Stress Scale score): for every unit increase in the ESS score, HbA1c increased by 0.143 g/dL (P < 0.001). CONCLUSION Subjective EDS was seen in approximately one-quarter of patients with diabetes in our population. There was a positive association between EDS and glycemic control. Screening of patients with diabetes for EDS should be part of routine diabetes management.
-
8.
Individual and diabetes presentation characteristics associated with partial remission status in children and adults evaluated up to 12 months following diagnosis of type 1 diabetes: An ADDRESS-2 (After Diagnosis Diabetes Research Support System-2) study analysis.
Humphreys, A, Bravis, V, Kaur, A, Walkey, HC, Godsland, IF, Misra, S, Johnston, DG, Oliver, NS
Diabetes research and clinical practice. 2019;:107789
-
-
Free full text
-
Abstract
AIMS: People with recently-diagnosed type 1 diabetes mellitus (T1D) may undergo a transient period of glycaemic control with less exogenous insulin. Identification of predictors of this 'remission' could inform a better understanding of glycaemic control. METHODS Participants in the ADDRESS-2 study were included who had 1 or 2 assessments of remission status (coincident insulin dose and HbA1c measurement, with remission defined by ≤0.4 units insulin/kg-body-weight/day with HbA1c < 53 mmol/mol). Demographic and clinical presentation characteristics were compared according to remission status and predictors of remission were explored by logistic regression analysis. RESULTS 1470 first and 469 second assessments of remission status were recorded within 12 months of diagnosis of T1D. Step increases in the probability of remission were identified at age-at-diagnosis 20 years and 3 months after diagnosis (both p < 0.001). Among those aged < 20 years, remission was associated with male gender (p = 0.02), no ketoacidosis (p = 0.02) and fewer than 2 symptoms at presentation (p = 0.004). None of these characteristics predicted remission in those aged ≥ 20 years. In the subgroup with two assessments, transition to remission was independently associated with first remission assessment in months 1-2 post-diagnosis (p = 0.01), with age-at-diagnosis ≥ 20 years (p = 0.01) and, in those aged < 20 years, with an early HbA1c of <57 mmol/mol. Adiposity, ethnicity, autoantibody status and other autoimmune disease were unrelated to remission. CONCLUSIONS For those diagnosed before 20 years of age, males, ketoacidosis-free, with fewer symptoms and low early HbA1c were more likely to experience remission, but remission was most likely in anyone aged ≥ 20 at diagnosis.
-
9.
Services satisfaction of type 2 diabetic patients attending Arar's diabetic center, Saudi Arabia.
Al Anazi, KS, Mohamed, AE, Hammad, SM
Saudi medical journal. 2019;(2):183-188
Abstract
To determine type 2 diabetic patients' satisfaction with the services provided by the Diabetic Center, Arar, Saudi Arabia, and to assess the relationship between patients' satisfaction and their diabetic control. Methods: An observational cross-sectional study, carried out in 322 patients at the Arar Diabetic Center, Arar, Kingdom of Saudi Arabia between January and April 2018. A systematic random sampling technique was applied to include every second type 2 diabetic patient attending the center. We interviewed the type 2 diabetic patients using a predesigned questionnaire tested for validity and reliability. Results: The mean age of the studied population was 48.5±13.05. The overall satisfaction rate was 65.8%. There was a significant association between patient satisfaction to both self-reported health status (p=0.001) and mode of treatment (p=0.02). Regarding service related factors: 78% of patients were satisfied with the time spent during consultation; 58.7% were satisfied with information given regarding the disease; 58.7% were dissatisfied with dietary advice; and 44.7% were dissatisfied with information given regarding medications. Hemoglobin A1c (HbA1c) was controlled in 64% of patients. There was a statistically significant association between patients' dissatisfaction and poor diabetic control. Conclusion: Two-thirds of the patients were satisfied with the services provided by the Diabetic Centres of Arar city, Saudi Arabia. The study recommends emphasis on patient education and addressing patient needs and worries.
-
10.
Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes.
Klonoff, D, Bode, B, Cohen, N, Penn, M, Geho, WB, Muchmore, DB
Diabetes care. 2019;(11):2154-2157
Abstract
OBJECTIVE Hepatic-directed vesicle insulin (HDV) uses a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin's hepatic biodistribution. We assessed HDV-insulin lispro (HDV-L) versus insulin lispro (LIS) in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Insulin Liver Effect (ISLE-1) was a 26-week, phase 2b, multicenter, randomized, double-blind, noninferiority trial. RESULTS Among 176 randomized participants (HDV-L n = 118, LIS n = 58), the difference in change from baseline A1C was 0.09% (95% CI -0.18% to 0.35%), confirming noninferiority (prespecified margin ≤0.4%). Overall, there were no statistically significant differences between treatments for hypoglycemia or insulin dosing. However, baseline A1C modified the treatment group effect (interaction P < 0.001) on clinically apparent hypoglycemia designated by treatment-blinded investigators as severe. Thus, at higher baseline A1C, there was less hypoglycemia and lower insulin dosing with similar A1C outcomes during HDV-L versus LIS, whereas greater risk of hypoglycemia despite similar A1C outcomes and insulin doses was observed with lower baseline A1C. Among poorly controlled participants (A1C ≥8.5%), incidence rates of severe hypoglycemia in the HDV-L and LIS arms were 69 and 97 events/100 person-years, respectively (P = 0.03), whereas with A1C <8.5%, respective rates were 191 and 21 events/100 person-years (P = 0.001). Similar A1C-dependent trends in hypoglycemia were seen with continuous glucose monitoring. Among poorly controlled participants, bolus insulin doses at end point were ∼25% lower with HDV-L (P = 0.02), despite similar A1C outcomes; in better-controlled participants, insulin doses and A1Cs were stable over time in both subgroups. No safety signals were identified. CONCLUSIONS Hepatic biodistribution of HDV-L appears to potentiate insulin effect in T1D, with divergent clinical outcomes in hypoglycemia dependent on baseline A1C.