Measures Of Glucose Variability Research Articles

Association of physical activity metrics with glucose variability in people with type 1 diabetes: A cross‐sectional study

AbstractThis study aims to investigate the association of physical activity metrics with measures of glucose variability in people with type 1 diabetes. From August 2019 to January 2022, people with type 1 diabetes, attending clinics or participating in ongoing research at the Dasman Diabetes Institute in Kuwait, were invited to participate in the study. Physical activity was measured over a 7‐day period using a wrist‐worn accelerometer, and glucose variability data were measured by continuous glucose monitoring (CGM) of the same period. Three hundred and eleven participants were recruited (age 33 (10) years, BMI 27(5) kg/m2 and n = 311 (169 female and 142 male)). Overall physical activity levels were not associated with any measure of glucose variability. The intensity gradient, which measures the distribution of physical activity intensity, was negatively associated with mean glucose (−1.01(−0.28, −1.74) and p = 0.007), CONGA (−1.00(−0.28, −1.72) and p = 0.007), J‐index (−11.7(−2.23, 21.2) and p = 0.016), HBGI (−2.73(−0.44, −5.02) and p = 0.020), GRADE (−2.27(−0.59, −3.95), p = 0.009) and GRADE – euglycaemia (−4.26(−0.46, −8.06) and p = 0–029) and the M‐value (−4.41 (−0.05, −8.77) and p = 0.049). Overall physical activity remains important, but it may be worth recommending people with type 1 diabetes to spend proportionately more of their day doing moderate to higher intensity physical activity, although this remains to be confirmed in an appropriately designed trial.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.

Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes

AimCardiac autonomic neuropathy (CAN) has been suggested to be associated with hypoglycemia and impaired hypoglycemia unawareness. We have assessed the relationship between CAN and extensive measures of glucose variability (GV) in patients with type 1 and type 2 diabetes. MethodsParticipants with diabetes underwent continuous glucose monitoring (CGM) to obtain measures of GV and the extent of hyperglycemia and hypoglycemia and cardiovascular autonomic reflex testing. ResultsOf the 40 participants (20 T1DM and 20 T2DM) (aged 40.70 ± 13.73 years, diabetes duration 14.43 ± 7.35 years, HbA1c 8.85 ± 1.70%), 23 (57.5%) had CAN. Despite a lower coefficient of variation (CV) (31.26 ± 11.87 vs. 40.33 ± 11.03, P = 0.018), they had a higher CONGA (8.42 ± 2.58 vs. 6.68 ± 1.88, P = 0.024) with a lower median LBGI (1.60 (range: 0.20–3.50) vs. 4.90 (range: 3.20–7.40), P = 0.010) and percentage median time spent in hypoglycemia (4 (range:4–13) vs. 1 (range:0–5), P = 0.008), compared to those without CAN. The percentage GRADEEuglycemia (3.30 ± 2.78 vs. 5.69 ± 3.09, P = 0.017) and GRADEHypoglycemia (0.3 (range: 0 – 3.80) vs. 1.8 (range: 0.9–6.5), P = 0.036) were significantly lower, while the percentage median GRADEHyperglycemia (95.45 (range:93–98) vs. 91.6 (82.8–95.1), P = 0.013) was significantly higher in participants with CAN compared to those without CAN. ConclusionCAN was associated with increased glycemic variability with less time in euglycemia attributed to a greater time in hyperglycemia but not hypoglycemia.

The association between time in the glucose target range and abnormal ankle-brachial index: a cross-sectional analysis

BackgroundTime in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes.MethodsWe retrospectively collected patients’ information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9–10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI.ResultsThe overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups.ConclusionsIn type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.

(Pre)diabetes, glycemia, and daily glucose variability are associated with retinal nerve fiber layer thickness in The Maastricht Study

Retinopathy and neuropathy in type 2 diabetes are preceded by retinal nerve fibre layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycaemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance. We used cross-sectional data from The Maastricht Study (up to 5455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycaemia (fasting plasma glucose [FPG], 2-h post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycaemia. After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95% CI], respectively − 0.16 [− 0.25; − 0.08]; − 0.05 [− 0.13; 0.03]; Ptrend = 0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP, but not CGM-assessed SD, were also associated with lower RNFL thickness (per SD, respectively − 0.05 [− 0.08; − 0.01]; − 0.06 [− 0.09; − 0.02]; − 0.05 [− 0.08; − 0.02]; − 0.04 [− 0.07; − 0.01]; − 0.06 [− 0.12; − 0.01]; and − 0.07 [− 0.21; 0.07]). In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycaemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycaemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of retinopathy and neuropathy.

686-P: Unstable Glucose Variability in Type 2 Diabetes Patients with Small Abdominal Visceral Fat Area and Impaired Endogenous Insulin Secretion

Background: Impaired endogenous insulin secretion was related to instability of glucose variability (GV) in patients with type 2 diabetes (T2DM) in our previous studies. However, some patients, including those with fasting serum C-peptide (CPR) ≤2 ng/mL, did not show this relationship. Given these findings, the present study aimed to identify other factors that affect GV in T2DM patients with impaired endogenous insulin secretion. Methods: Data were obtained from our prospective observational study, comprising 2Japanese outpatients with T2DM who underwent continuous glucose monitoring (CGM) , fasting blood sample collection, and a computed tomography scan of their abdominal visceral and subcutaneous fat. Fasting CPR was used as a marker of endogenous insulin secretion and the coefficient of variation (CV) for the CGM data was used as a measure of GV. Background characteristics related to unstable GV were identified by multivariate logistic regression analysis after we extracted the data for patients with T2DM and CPR ≤2 ng/mL. All tests were two-sided. P&amp;lt;0.was considered to indicate statistical significance. Results: In the total cohort, mean age was 67.0 (IQR 58.0, 74.8) years, mean HbA1c 7.1% (IQR 6.6%, 7.7%) , and mean body mass index (BMI) 25.0 (IQR 23.0, 28.4) kg/m2. In patients with low CPR (≤2 ng/mL; n=119) , small visceral fat area (VFA) was an independent risk factor for CV above the median CV (OR 0.98, 95% CI 0.97-0.99, P=0.0443) , while subcutaneous fat area (SFA) and BMI were equally distributed. In patients with high CPR (&amp;gt;2 ng/mL; n=85) , VFA, SFA, and BMI were equally distributed between patients with CV above or below the median CV. Conclusions: GV is unstable in T2DM patients with impaired endogenous insulin secretion, particularly in patients with small VFA. The present findings suggest that visceral fat is related to the stability of GV. Disclosure A.Miya: None. A.Nakamura: Research Support; Kissei Pharmaceutical Co., Ltd., MSD, Nippon Boehringer Ingelheim, Taisho Pharmaceutical Holdings Co., Ltd. H.Nomoto: None. H.Kameda: None. K.Cho: None. S.Nagai: Other Relationship; Eli Lilly and Company. Y.M.Ito: None. H.Miyoshi: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Company, Ltd., LifeScan, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Speaker’s Bureau; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kowa Company, Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. T.Atsumi: Consultant; AbbVie Inc., AstraZeneca, MEDICAL &amp; BIOLOGICAL LABORATORIES CO., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Research Support; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Speaker’s Bureau; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, UCB, Inc.

Abstract 9888: Ischemic Heart Disease and Type 2 Diabetes Complications Are Associated with Glycemic Variability Measured by Continuous Glucose Monitoring

Introduction: The management of type 2 diabetes mellitus (DM) has focused on achieving normal glucose levels in order to prevent cardiovascular disease (CVD) and other DM-related complications. Some have suggested that glucose variability (GV) may be associated with DM complications. Other studies, using manual glucose testing, failed to prove it. In our retrospective study using a large administrative database and thousands of patients wearing continuous glucose monitors (CGM), we evaluated the association between various glucose parameters and CVD and DM complications. Methods: Of 15,815 people enrolled in a T2DM program who ordered a CGM device, 58.2% actually used it. The final cohort had 4,530 CGM users with &gt; 30 days of CGM data within 90 days. Metrics included mean glucose and GV measures such as SD, IQ range, % coefficient of variation (%CV), mean amplitude of glycemic excursions (MAGE) and time in range. A multivariable regression analysis tested for the association between these metrics and the occurrence of CVD and DM complications based on claims from Jan 2016 through April 2021. Results: The mean age was 53, with a 1:1 gender ratio. Mean glucose level was 157 (SD + 32). At least one CVD condition or DM complication (nephro-, retino-, neuropathy, skin ulcer/gangrene, circulatory problems) was present in 84% of subjects. The 2 most frequent were ischemic heart disease (IHD) in 15.7% and DM kidney disease in 9.5%. Subjects with IHD or DM complications had significantly higher mean glucose and GV measures (p&lt;0.001). However, there was a 10-fold difference between a marker of variability (%CV) and the mean glucose level: for every % point increase in %CV there was a 7% increased likelihood of DM complications, compared with only a 0.7% increase for every additional 1 mg/dl of mean glucose. Conclusions: In a relatively young cohort of persons with T2DM wearing CGM, glycemic variability, as measured by %CV, was more strongly associated with IHD and diabetic complications than mean glucose level. This suggests that management of diabetes should focus more on glycemic variability than absolute glucose levels. Wider adoption of CGM may more effectively detect persons with high glycemic variability at risk for ischemic heart disease and other diabetic complications.

546-P: Effects of Metformin on Heart Rate Variability in Adolescents with Type 1 Diabetes: A Secondary Analysis of a Randomized Crossover-Controlled Trial

Aims: Metformin might improve glycemic control in patients with T1D, but whether it has cardiovascular benefit is controversial. We aimed to investigate whether metformin improved cardiac autonomic neuropathy, as measured by heart rate variability (HRV), in patients with T1D. Methods: This is a secondary analysis of a crossover, randomized trial conducted in adolescents with T1D inadequately controlled with insulin. Patients were randomly received metformin added on insulin for 24 weeks followed by insulin treatment alone for a subsequent 24 weeks or vice versa. The mean amplitude of glycemic excursions (MAGE) was obtained from CGM as a measure of glucose variability, while SD of beat-to-beat (NN) intervals (SDNN), SD of the average NN intervals calculated over 5 minutes (SDANN), the percentage of the interval differences of successive NN intervals greater than 50 ms (PNN50), the square root of the mean squared differences of successive NN intervals (RMSSD), low-frequency (LF) and high frequency (HF) power were assessed by 24-h Holter monitoring as measures of HRV. Results: Seventeen patients with age 14.4±2.3 years, BMI 18.2±1.8 kg/m2, T1D duration 5.4±3.2 years and HbA1c 9.2±1.6% were enrolled. Changes in HbA1c, BMI, lipid profiles and MAGE were similar between groups. Compared with insulin monotherapy, metformin added on insulin markedly increased SDNN (between group difference [SE], 26.96 [11.77], P=0.034), SDANN (25.62 [12.12], P= 0.049), pNN50 (10.14 [3.05], P= 0.003) and HF (236.08 [83.21], P= 0.01). Changes in RMSSD and LF were not different between groups. In a multivariable regression analysis, the increase in SDNN remained significant after adjusting for ΔHbA1c, ΔMAGE and Δ systolic blood pressure (SBP) (β= 28.62, P= 0.039), suggesting the independent effect of metformin on SDNN. Conclusions: In adolescent patients with T1D, metformin increased HRV despite no obvious effect on improvement in metabolic parameters. Disclosure D. Yang: None. W. Xu: None. H. Deng: None. J. Lv: None. J. Yan: None. B. Yao: None. J. Weng: None. Funding National Key Research and Development Program of China (2017YFC1309602); Science and Technology Planning Project of Guangdong Province (2017A020215142); Natural Science Foundation of Guangdong Province (2019A1515010979)

Effects of glucose variability on hematopoietic stem/progenitor cells in patients with type 1 diabetes.

Diabetes reduces the levels of hematopoietic stem/progenitor cells (HSPCs), which can contribute to organ and tissue homeostasis. Among patients with diabetes, lower HSPC levels predict the development or worsening of micro- and macro-angiopathy. High glucose variability is also associated with diabetic complications and we have previously shown that acute hypoglycaemia can stimulate stem/progenitor cells. Thus, we evaluated the relationship between glucose variability or time in hypoglycaemia and HSPCs in patients with type 1 diabetes (T1D). Patients with T1D were compared to healthy subjects. HSPCs (CD34+, CD133+, CD34+CD133+, CD34 + CD45dim) were quantified by flow cytometry. Using flash glucose monitoring system for 90days, we calculated several measures of glucose variability and time in hypoglycaemia. Forty-four patients with T1D and 44 healthy subjects were enrolled. Compared to healthy controls, T1D patients had significantly lower levels of HSPCs and duration of diabetes was inversely correlated with HSPC levels. Significant direct correlations were found between HSPC levels and the coefficient of variation of glucose levels or time in hypoglycaemia, which were stronger in patients with short-term than in those with long-standing diabetes. This study confirms the pauperization of HSPCs in T1D patients and demonstrates a potential HSPC-stimulatory effect of hypoglycaemia, which mitigates with long-lasting diabetes. These data are consistent with a model whereby disease chronicity progressively blunts the release of HSPCs in response to adrenergic triggers, like hypoglycaemic events.

Continuous glucose monitoring to assess glycemic control in the first 6 weeks after pancreas transplantation.

Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT. We investigated GV using continuous glucose monitoring (CGM) 3-6weeks after PT. Eleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5±13.9, PAK 119.9±12.8, and PTA 131.1±29mg/dL (P value .6). Percentage of time in range (TIR, 70-180mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70mg/dL. Percentage >180mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients. All 3 types of PT resulted in excellent glucose control 3-6weeks post-procedure. CGM outcomes represent an important objective outcome after PT.

Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study.

Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.

SAT-LB025 Analysis of Benefit/Risk in the Subgroup of Patients with BMI of &gt;=27 Kg/m2 in the Dapagliflozin DEPICT-1 and -2 Trials in Type 1 Diabetes

Sodium glucose co-transporter-2 inhibitor (SGLT-2i) adjunct therapies have been studied in phase 3 programs for use in people with type 1 diabetes (T1D) and are currently under regulatory review for approval in adults in North America, Europe, and Japan. The DEPICT-1 and -2 programs assessed dapagliflozin (DAPA) 5 and 10 mg in adults with T1D. Treatment with DAPA in people with T1D resulted in important benefits with a manageable risk profile, though there was a higher incidence of events adjudicated as definite DKA in those receiving DAPA. During the 52-week study period, in the total population, the proportion of patients with events adjudicated as definite DKA events was 4.0% and 1.1% in the DAPA 5 mg and PBO groups, with incidence rates of 4.6 and 1.3 per 100 patient years, respectively. However, in the subgroup of patients with BMI ≥27 kg/m², the proportion of patients with events adjudicated as definite DKA was reduced to 1.8% and 1.0%, with incidence rates per 100 patient-years of 1.9 and 1.2 in the DAPA 5 mg and PBO groups, respectively. Efficacy endpoint results for the subgroup with BMI ≥27 kg/m2 were similar to the overall population. After 24 weeks of treatment, HbA1c decreased from a baseline mean of 8.43 to 7.98% in the 5 mg group vs. 8.40 to 8.38% for PBO, with a PBO-corrected difference of –0.43% (95% CI –0.55, –0.31). Mean insulin dose decreased from 72.07 to 64.65 IU in the 5 mg group vs. 70.90 to 70.37 IU for PBO, with a PBO-corrected difference of –10.24 IU (95% CI –13.52, –6.84). Mean body weight decreased from 91.22 to 88.54 kg in the 5 mg group vs. 92.89 to 93.15 kg for PBO, with a PBO-corrected difference of –2.89 kg (95% CI –3.43, –2.36). As assessed by continuous glucose monitoring, mean interstitial glucose decreased from 192.52 to 176.19 mg/dL in the 5 mg group vs. 191.25 to 192.38 mg/dL for PBO, with a PBO-corrected difference of –16.81 mg/dL (95% CI –21.37, –12.25). Mean amplitude of glycemic excursions, a measure of glucose variability, decreased from 169.10 to 148.78 mg/dL in the 5 mg group vs. 164.94 to 163.71 mg/dL for PBO, with a PBO-corrected difference of –17.48 mg/dL (95% CI –22.28, –12.67). Mean time in the target glycemic range (glucose >70 and <180 mg/dL) increased from 44.17% to 53.65% in the 5 mg group vs. 44.67% to 44.44% for PBO, with a PBO-corrected difference of +9.69% (95% CI +7.61, +11.77) without increasing time in a hypoglycemic state (glucose <70 mg/dL). The proportion of patients achieving a reduction in HbA1c ≥0.5% without experiencing severe hypoglycemia was 47.2% in the 5 mg group vs. 21.3% for PBO, with 3.52 (95% CI 2.39, 5.21) greater odds of achieving this endpoint in those receiving 5 mg. In summary, while the benefit/risk profile of DAPA is favorable in the entire T1D study population, in this post-hoc analysis the benefit/risk appeared to be further enhanced in the subgroup of patients with BMI ≥27 kg/m² receiving DAPA 5 mg. Funded by AstraZeneca. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus.

Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24-h day. Our aim was to examine the role of temporal glucose variation on the development of large for gestational age (LGA) infants in women with treated gestational diabetes mellitus (GDM). We performed a prospective observational study of 162 pregnant women with GDM in specialist multidisciplinary antenatal diabetes clinics. Participants undertook 7-day masked CGM at 30-32 weeks' gestation. Standard summary indices and glycemic variability measures of CGM were calculated. Functional data analysis was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity, and parity. Mean glucose was significantly higher in women who delivered an LGA infant (6.2 vs. 5.8 mmol/L, P = 0.025, or 111.6 mg/dL vs. 104.4 mg/dL). There were no significant differences in percentage time in, above, or below the target glucose range or in glucose variability measures (all P > 0.05). Functional data analysis revealed that the higher mean glucose was driven by a significantly higher glucose for 6 h overnight (0030-0630 h) in mothers of LGA infants (6.0 ± 1.0 mmol/L vs. 5.5 ± 0.8 mmol/L, P = 0.005, and 108.0 ± 18.0 mg/dL vs. 99.0 ± 14.4 mg/dL). Mothers of LGA infants run significantly higher glucose overnight compared with mothers without LGA infants. Detecting and addressing nocturnal glucose control may help to further reduce rates of LGA in women with GDM.

Is there an association between non-dipping blood pressure and measures of glucose variability in type 1 diabetes?

AimTo assess the relationship between glucose variability (GV) and non-dipping of blood pressure (BP) as a marker of cardiovascular autonomic neuropathy (CAN) among patients with type 1 diabetes (T1D). MethodsForty-one subjects with T1D (age 34 ± 13 years, duration 13 ± 6 years, HbA1c 8 ± 1.2%) without cardiovascular disease, dyslipidemia, or hypertension at baseline were enrolled in a 3-year observational cohort study. Subjects were phenotyped for CAN with heart rate variability, cardiovascular autonomic reflex tests, and 24-h BP profiles at baseline and during follow-up. Non-dipping was defined as nocturnal systolic and diastolic BP fall of ≤10%. Reverse dipping BP was defined as a <0% change in the day to night for systolic and diastolic BP. Indices of GV were derived from 5-day continuous glucose monitoring obtained at 3-month intervals, and serum inflammatory biomarkers in all subjects. ResultsAt baseline 10% of the T1D subjects were non-dippers. The dippers and non-dippers were similar in age, diabetes duration, glucose control, traditional cardiovascular risk factors, GV and inflammatory markers. No significant correlations were found at baseline between non-dipping nocturnal blood pressure and measures of GV. At 3 years there were no differences in risk factor profile of subjects who were non-dippers over time (progressors) and those who were dippers (non-progressors). ConclusionIn a cohort of contemporary patients with T1D following the current standard of care in diabetes, the prevalence of non-dipping is relatively low. There were no clear phenotypes that explained the difference in the risk for non-dipping, including GV. Ambulatory blood pressure monitoring could be used as a tool for improved CVD risk stratification and development of therapeutic interventions in these patients.

Glycemic Variability from CGM Correlates with Indices of Glucose Metabolism in Healthy Obesity but Not in Type 2 Diabetes

We evaluated the relationship between measurements of beta cell function and insulin resistance assessed from OGTT and 2-step glucose clamp data with indices of glucose variability (GV) obtained with a continuous glucose monitor (CGM) in obese subjects with and without type 2 diabetes (T2D). 17 healthy obese (OB) (FPG 91 ± 4.9mg/dl and A1c 5.2 ± 0.4%) and 8 age- and weight-matched participants with T2D treated with diet and/or metformin (FPG 131.5 ± 42.8 mg/dl and A1c 6.8 ± 0.8%) wore CGM (Dexcom®) for up to 5 days. EasyGV® software was used to calculate indices of GV: standard deviation (SD), mean amplitude of glycemic excursions (MAGE), J-Index, continuous overlapping net glycemic action (CONGA), and Glycemic Risk Assessment in Diabetes Equation (GRADE). Indices of glucose metabolism were determined with a 2 hour OGTT and a two-step hyperglycemic-euglycemic clamp. Insulin levels during the hyperglycemic-step of clamp (116 ± 126 vs. 40 ± 23 mU/mL) were equal in both groups, while glucose infusion rate (GIR) (7.7 ± 3.1 vs. 3.9 ± 2.4 mg/kg/minutes) during euglycemia was as expected significantly lower in the T2D subjects compared to OB subjects. GV indices (SD, CONGA, J-Index, GRADE) were statistically lower in OB vs. T2D (P&amp;lt;0.05). Insulin Sensitivity Index (ISI0-120) and the insulin secretion-sensitivity index-2 (ISSI-2) were also lower in obese than in T2D subjects (P&amp;lt;0.001). CGM indices (mean, CONGA, J-index, and GRADE) correlated with incremental AUC of insulin during the OGTT, but not for glucose; as well as insulin levels during the hyperglycemic-step (r=0.740, P&amp;lt;0.01), and GIR during the euglycemic step of the clamp (r= -0.733, P&amp;lt;0.01). CGM measures of GV (CONGA, J-Index, and GRADE) were lower in obese compared to T2D subjects. These results suggest that GV indices are surrogate measurements of beta cell function and insulin action in obese subjects, and may help determine progression to T2D. Disclosure A. Elshafie: None. W. Lam: None. L. Parikh: None. E. Sanchez Rangel: None. C.P. Schmidt: None. J. Hwang: None. C.W. Yeckel: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc..

Effect of Oral Pre-Meal Administration of Betaglucans on Glycaemic Control and Variability in Subjects with Type 1 Diabetes.

We conducted a double-blind placebo-controlled crossover pilot study to investigate the effect of oat betaglucans (β-glucan) on glycaemic control and variability in adults with type 1 diabetes (T1D; n = 14). Stomacol® tablets (1.53 g of β-glucan) or placebo (Plac) were administered three times daily before meals for two weeks. Glucose levels were monitored during the second week by continuous glucose monitoring (CGM). There was an increase in basic measures of glycaemic control (maximal glucose value 341 ± 15 vs. 378 ± 13 mg/dL for Plac and β-glucan, p = 0.004), and average daily risk range (62 ± 5 vs. 79 ± 4 mg/dL for Plac and β-glucan, p = 0.003) favouring Plac over β-glucan, but no increase in the M-value (the weighted average of the glucose values) or other more complex measures. Basic measures of glucose variability were also slightly increased during β-glucan treatment, with no difference in more complex measures. However, glycaemic variability increased between the first and last two CGM days on Plac, but remained unchanged on β-glucan. In conclusion, in this pilot study we were unable to demonstrate a general positive effect of β-glucan before meals on glucose control or variability in T1D.

An α-glucosidase inhibitor could reduce T-wave alternans in type 2 diabetes patients

BackgroundWe tested the hypothesis that an alpha-glucosidase inhibitor (α-GI), miglitol, is effective in protecting the cardiovascular system in type 2 diabetes mellitus (T2DM). MethodsWe studied 19 hospitalized heart disease patients with T2DM in whom we performed continuous glucose monitoring, Holter electrocardiogram, and ambulatory blood pressure (BP) monitoring simultaneously for 48h. The α-GI miglitol was administered for half of the study period by a cross-over fashion. T-wave alternans (TWA), a marker of future fatal arrhythmic events, was also analyzed by Holter ECG. ResultsOf the 19 patients, the measures of glucose variability were significantly lower during miglitol therapy than in control period. BP variability was similar with/without miglitol. However, TWA was significantly lower during the miglitol period compared to control period (63±4.8 vs. 75.8±5.1μV, p=0.032). ConclusionAn α-GI, miglitol, can reduce TWA by reducing the fluctuation of glucose in heart disease patients with T2DM.

Metrics for glycaemic control - from HbA1c to continuous glucose monitoring.

As intensive treatment to lower levels of HbA1c characteristically results in an increased risk of hypoglycaemia, patients with diabetes mellitus face a life-long optimization problem to reduce average levels of glycaemia and postprandial hyperglycaemia while simultaneously avoiding hypoglycaemia. This optimization can only be achieved in the context of lowering glucose variability. In this Review, I discuss topics that are related to the assessment, quantification and optimal control of glucose fluctuations in diabetes mellitus. I focus on markers of average glycaemia and the utility and/or shortcomings of HbA1c as a 'gold-standard' metric of glycaemic control; the notion that glucose variability is characterized by two principal dimensions, amplitude and time; measures of glucose variability that are based on either self-monitoring of blood glucose data or continuous glucose monitoring (CGM); and the control of average glycaemia and glucose variability through the use of pharmacological agents or closed-loop control systems commonly referred to as the 'artificial pancreas'. I conclude that HbA1c and the various available metrics of glucose variability reflect the management of diabetes mellitus on different timescales, ranging from months (for HbA1c) to minutes (for CGM). Comprehensive assessment of the dynamics of glycaemic fluctuations is therefore crucial for providing accurate and complete information to the patient, physician, automated decision-support or artificial-pancreas system.

Glucose Variability Measures as Predictors of Oral Feeding Intolerance in Acute Pancreatitis: A Prospective Pilot Study.

Oral feeding intolerance (OFI) is a common complication in patients with acute pancreatitis (AP). Variations in blood glucose are associated with impaired gastrointestinal function but, to date, measures of glucose variability have not been investigated to predict OFI in patients with AP. To investigate the usefulness of several glucose variability measures in predicting the occurrence of OFI early in the course of AP. In this prospective cohort study, six measures of glucose variability were calculated prior to the occurrence of OFI. Multivariate binary logistic regression analyses were conducted, and the diagnostic performance and accuracy of glucose variability measures were assessed. Of the 95 prospectively enrolled patients, 21 (22%) developed OFI. After adjusting for confounders, admission blood glucose concentration and mean blood glucose concentration were significantly associated with OFI [odds ratio 1.49 (95% confidence interval 1.01-2.20) and odds ratio 1.67 (95% confidence interval 1.07-2.61), respectively]. Both admission blood glucose and mean blood glucose had an area under the curve of 0.83 and positive likelihood ratios of 6.45 and 10.19, respectively. Blood glucose concentration before refeeding, standard deviation of blood glucose concentration, coefficient of variation, and mean amplitude of glycemic excursions were not significantly associated with OFI. In-hospital blood glucose concentrations are associated with subsequent development of OFI in patients with AP. In particular, admission blood glucose and mean blood glucose could be useful predictors of OFI in this setting.

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BackgroundWomen with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy.Methods/designA multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5–7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes.DiscussionThis will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes.Trial registrationClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-0961-5) contains supplementary material, which is available to authorized users.