Lower Glucose Variability Research Articles

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report

BackgroundType 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis.Case presentationA 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with “indeterminate colitis” and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis.ConclusionsOur patient’s improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an ‘insulin free T1D’, our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Comparison of Metabolic Control in Children and Adolescents Treated with Insulin Pumps.

While insulin pumps remain the most common form of therapy for youths with type 1 diabetes (T1DM), they differ in the extent to which they utilize data from continuous glucose monitoring (CGM) and automate insulin delivery. The aim of the study was to compare metabolic control in patients using different models of insulin pumps. This retrospective single-center study randomly sampled 30 patients for each of the following treatments: Medtronic 720G without PLGS (predictive low glucose suspend), Medtronic 640G or 740G with PLGS and Medtronic 780G. In the whole study group, we used CGM systems to assess patients' metabolic control, and we collected lipid profiles. In three groups of patients, we utilized CGM sensors (Guardian 3, Guardian 4, Libre 2 and Dexcom G6) to measure the following glycemic variability proxy values: time in range (TIR), time below 70 mg/dL (TBR), time above 180 mg/dL (TAR), coefficient of variation (CV) and mean sensor glucose. Medtronic 640G or 740G and 780G users were more likely to achieve a target time in the target range 70-180 mg/dL (≥80%) [Medtronic 720G = 4 users (13.3%) vs. Medtronic 640G/740G = 10 users (33.3%) vs. Medtronic 780G = 13 users (43.3%); p = 0.0357)] or low glucose variability [Medtronic 720G = 9 users (30%) vs. Medtronic 640G/740G = 18 users (60%) vs. Medtronic 780G = 19 users (63.3%); p = 0.0175)]. Any integration between the insulin pump and CGM was associated with better glycemic control. More advanced technologies and artificial intelligence in diabetes help patients maintain better glycemia by eliminating various factors affecting postprandial glycemia.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

Short-term glucose variability as a determinant of the healing rate of diabetic foot ulcer: A retrospective study

BackgroundThe aim of this study was to describe the clinical characteristics of people with diabetic foot ulcer (DFU) according to glucose variability (GV) and to investigate the relationship between GV and DFU outcome in a population with type 2 diabetes (T2D) and DFU. MethodsThis is a retrospective study of 300 individuals aged 64.3 years (181 males) treated for DFU in a tertiary-care center with a regular follow-up for 6 months. Laboratory measurements and clinical assessments were collected at baseline. According to the coefficient of variation (CV) cut-off (≥36%), people were divided into two groups (low and high GV). ResultsCompared with low GV group (n = 245), high GV group (n = 55) had significant longer duration of diabetes [low vs high GV, mean ± Standard Deviation (SD), 17.8 ± 11.8 vs 22.4 ± 10.8, P = 0.012], higher levels of glycated haemoglobin [median (IQR), 7.4 (6.6, 8.8) vs 8.2 (7.0, 9.6), P = 0.010] and urinary albumin excretion [25.2 (11.9, 77.0) vs 48.0 (23.2, 106.0), P = 0.031]. Moreover, 10 days self-monitoring of blood glucose-derived glycemic metrics were significantly different between groups. No differences among clinical features were found. The multiple logistic regression analysis identified CV and SD as negative predictors of healing. ConclusionsIn a population of people with T2D and DFU treated in a tertiary-care center, individuals with high GV had a 3-fold higher risk of healing failure, as compared with those with low GV. CV and SD were related to poor healing within 6 months follow-up.

Slowing of Peripheral Nerve Conduction Velocity in Children and Adolescents With Type 1 Diabetes Is Predicted by Glucose Fluctuations.

There is a strong need for the better identification of early subclinical manifestations of microvascular complications, such as diabetic peripheral neuropathy, in young individuals with diabetes. To identify peripheral neuropathy and contributing factors at an asymptomatic disease stage, and to exclude height as a known modifying factor, we performed association studies of height-adjusted nerve conduction velocity. We identified high glucose variability, especially the SD of mean glucose, as an unexpectedly strong predictor of slowed nerve conduction velocity. More attention should be paid to the goal of low glucose variability in the care of individuals with diabetes.

Characteristics of glucose variability in different types of diabetes mellitus in young patients

Introduction. Rare types of diabetes mellitus including MODY (Maturity-Onset Diabetes of the Young) are quite complicated to verification and differential diagnosis. That is often leads to diagnostic delays, medical errors in choosing treatment tactics. This kind of event could aggravate the course of the disease and must be prevented.Aim. Evaluation the characteristics of glucose variability (GV) in different types of diabetes mellitus (DM) in young people using continuous glucose monitoring (CGM) systems is necessary to understand the diagnostic value of the method.Materials and methods. We studied 72 patients with clinical signs of MODY who underwent a molecular genetics study to verify the type of DM. According to the results of the study, patients were divided into 3 groups: with genetically confirmed MODY2 (n = 31), MODY3 (n = 16); comparison group consists of the patients with type 2 diabetes (n = 25). All patients at the second stage underwent CGM for 14 days. At the third stage, the obtained patterns of glycemia were presented in the form of GV indices using the GLINVA program, and an in-depth analysis of glucose variability was performed.Results. Some features in the characteristics of the glycemic profile in young people with monogenic forms of DM were noticed. It was determined that in MODY2 the level of fasting plasma glucose (FPG) (p = 0.004) and HbA1c (p = 0.010) was significantly lower than in MODY3, and low GV was determined during the day, which probably causes a lower incidence of diabetic complications than other types of diabetes. In individuals with MODY3, higher FPG and HbA1c values were found, in contrast to MODY2 and type 2 diabetes. MODY3 profile is characterized with significantly higher GV and longer time spent above the target ranges (compared to type 2 diabetes).Conclusions. The approach to evaluate the glycemic profile used in the study is modern and affordable. It could become a tool for determining criteria for diagnosing the type of diabetes in patients with clinical manifestations of MODY.

Continuous Glucose Monitoring in Patients Following Simultaneous Pancreas-Kidney Transplantation: Time in Range and Glucose Variability.

Simultaneous pancreas-kidney transplantation (SPKT) can improve long-term patient survival and restore endogenous insulin secretion in recipients with type 1 diabetes (T1D). There are currently few data on glucose fluctuations assessed by continuous glucose monitoring (CGM) after SPKT. Aim: to evaluate CGM-derived time in range (TIR) and glucose variability (GV) in patients with T1D and functioning pancreatic grafts after SPKT. Fifty-four CGM recordings from 43 patients, 15 men and 28 women, aged 34 (31; 39) years were analyzed. Time since SKPT was up to 1 year (group 1, n = 13), from 1 to 5 years (group 2, n = 15), and from 5 to 12 years (group 3, n = 26). TIR (3.9-10 mmol/L), Time Above Range (TAR), Time Below Range (TBR), and GV parameters were estimated. There were no differences in mean glucose (5.5 [5.1; 6.2], 5.9 [5.4; 6.2], and 5.9 [5.6; 6.7] mmol/L), TIR (97.6 [92.8-99.1], 97.2 [93.2; 99.1], and 97.5 [93.4; 99]%); TAR (0, 1.8 [1.3; 3.7], and 2.5 [2; 5]%), TBR (5 [3.3; 12.7], 4.1 [2.2; 10.1], and 3.5 [1.3; 6.5]%) and GV parameters between three groups (all p > 0.05). Thus, recipients with functioning pancreatic grafts demonstrate remarkably high TIR and low GV after SPKT.

Making sense of weekly insulins

The current issue of The Lancet Diabetes & Endocrinology sees publication of a phase 2 study of the weekly insulin under development from Eli Lilly. 1 Frias J Chien J Zhang Q et al. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study. Lancet Diabetes Endocrinol. 2023; (published online Feb 6.)https://doi.org/10.1016/S2213-8587(22)00388-6 Google Scholar Phase 2 studies have also been published from Novo Nordisk, who have further announced top-line results of a series of phase 3 studies to investors. 2 Rosenstock J Bajaj HS Janež A et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020; 383: 2107-2116 Crossref PubMed Scopus (77) Google Scholar Once-daily basal insulin is the standard starter regimen in people with type 2 diabetes, 3 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (20) Google Scholar and experience with other once-weekly injectables in people with type 2 diabetes, notably of GLP-1 receptor agonists, 4 Holleman C Hopcroft A Close K 3Q22 GLP-1 industry roundup. www.closeconcerns.com/knowledgebase/r/db4d2bb8Date: Nov 15, 2022 Date accessed: December 2, 2022 Google Scholar is of market preference over once-daily preparations; it is probable that clinical practice will adopt licensed weekly insulins very quickly. Weekly basal insulin might be of less relevance to people with type 1 diabetes, for whom multiple meal-time insulin doses will still be needed. Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 studyWeekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Full-Text PDF

Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study

The burden of daily basal insulins often causes hesitancy and delays in the initiation of insulin therapy. Basal insulin Fc (BIF, insulin efsitora alfa), designed for once-weekly administration, is a fusion protein combining a novel single-chain insulin variant with a human immunoglobulin G (IgG) Fc domain. In this study, we explored the safety and efficacy of BIF in people with type 2 diabetes who had been previously treated with basal insulin. For this phase 2, 44-site (clinical research centres and hospitals), randomised, open-label, comparator-controlled, 32-week study in the USA, Puerto Rico, and Mexico, we enrolled participants with type 2 diabetes. Eligible participants had to be adults (aged ≥18 years) and to have been treated with basal insulin and up to three oral antidiabetic medicines. Participants were randomly assigned (1:1:1) to subcutaneous administration of BIF (BIF treatment group 1 [BIF-A1] or 2 [BIF-A2]) or insulin degludec. Randomisation was stratified by country, baseline HbA1c values (<8·5% or ≥8·5%; <69·4 or ≥69·4 mmol/mol), use of sulfonylureas (yes or no), and baseline BMI (<30 or ≥30 kg/m2). The randomisation scheme was performed using an interactive web-response system, which ensured balance between treatment groups. Different fasting glucose targets for the BIF-A1 (≤7·8 mmol/L or ≤140 mg/dL; titrated every 2 weeks), BIF-A2 (≤6·7 mmol/L or ≤120 mg/dL; titrated every 4 weeks), and degludec (≤5·6 mmol/L or ≤100 mg/dL) groups were selected. Patients randomly assigned to BIF received a one-time loading dose ranging from 1·5-3 times their calculated weekly dose. The first weekly dose was administered 1 week after the loading dose. We used interstitial fasting glucose measurements from the Dexcom G6 continuous glucose monitoring system to titrate the basal insulin. The primary measure of glycaemic control was change in HbA1c from baseline to week 32 for BIF. BIF was also compared with degludec (with a non-inferiority margin of 0·40%). The efficacy analysis set consisted of data from all randomised study participants who received at least one dose of the study medication and participants were analysed according to the treatment they were assigned. The safety population was the same as the efficacy analysis set. The completed trial is registered at ClinicalTrials.gov (NCT03736785). Between Nov 15, 2018 and Feb 18, 2020, 399 participants were enrolled and randomised to BIF-A1 (n=135), BIF-A2 (n=132), or degludec (n=132); 202 (51%) were female and 197 (49%) were male. 379 were analysed for the primary outcome (BIF-A1: n=130; BIF-A2: n=125; degludec: n=124). Mean HbA1c change from baseline to week 32, the primary outcome, was -0·6% (SE 0·1%) for BIF-A1 and BIF-A2. Degludec achieved a change from baseline of -0·7% (0·1%). The pooled BIF analysis achieved non-inferiority versus degludec for the treatment difference in HbA1c (0·1% [90% CI -0·1 to 0·3]). The hypoglycaemia (≤3·9 mmol/L or ≤70 mg/dL) event rates (hypoglycaemia events per patient per year) in the BIF groups were 25% lower than those in the degludec group (treatment ratio BIF-A1 vs degludec was 0·75 [0·61-0·93]; and BIF-A2 vs degludec was 0·74 [0·58-0·94]). BIF was well tolerated; treatment-emergent adverse events were similar across groups. Weekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Eli Lilly and Company.

Importance of beta cell mass for glycaemic control in people with type 1 diabetes

Aims/hypothesisThe role of beta cell mass in the balance of glucose control and hypoglycaemic burden in people with type 1 diabetes is unclear. We applied positron emission tomography (PET) imaging with radiolabelled exendin to compare beta cell mass among people with type 1 diabetes and either low glucose variability (LGV) or high glucose variability (HGV).MethodsAll participants with either LGV (n=9) or HGV (n=7) underwent a mixed-meal tolerance test to determine beta cell function and wore a blinded continuous glucose monitor for a week. After an i.v. injection with [68Ga]Ga-NODAGA-exendin-4, PET images were acquired for the quantification of pancreatic uptake of radiolabelled exendin. The mean standardised uptake value (SUVmean) of the pancreas was used to determine the amount of beta cell mass.ResultsParticipants with LGV had lower HbA1c (46.0 mmol/mol [44.5–52.5] [6.4% (6.3–7)] vs 80 mmol/mol [69.0–110] [9.5% (8.5–12.2)], p=0.001) and higher time in range (TIR) (75.6% [73.5–90.3] vs 38.7% [25.1–48.5], p=0.002) than those with HGV. The SUVmean of the pancreas was higher for the LGV than for the HGV group (5.1 [3.6–5.6] vs 2.9 [2.1–3.4], p=0.008). The AUCC-peptide:AUCglucose ratio was numerically, but not statistically, higher in the LGV compared with the HGV group (2.7×10−2 [6.2×10−4–5.3×10−2] vs 9.3×10−4 [4.7×10−4–5.2×10−3], p=0.21). SUVmean correlated with the AUCC-peptide:AUCglucose ratio (Pearson r=0.64, p=0.01), as well as with the TIR (r=0.64, p=0.01) and the SD of interstitial glucose levels (r=−0.66, p=0.007).Conclusion/interpretationOur data show higher beta cell mass in people with type 1 diabetes and LGV than in those with HGV, independent of beta cell function.Graphical abstract

Preserved C-peptide secretion is associated with higher time in range (TIR) on intermittently scanned continuous glucose monitoring in Chinese adults with type 1 diabetes.

To explore the relationship between C-peptide secretion and time in range (TIR) in adult patients with type 1 diabetes. From December 2018 to December 2020, 76 type 1 diabetes participants were enrolled from the Department of Endocrinology and Metabolism of Peking University People's Hospital. All participants wore intermittently scanned continuous glucose monitoring (isCGM), and insulin dosage was adjusted according to standardized clinical procedures. Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10-200 pmol/L) based on fasting serum C-peptide levels. Differences of TIR, metrics related to glucose variability and hypoglycemic events were compared. A total of 94,846 isCGM values obtained from 39 male and 37 female participants were analyzed. Individuals with preserved C-peptide secretion had shorter diabetes duration (2.0 (0.5, 10.0) vs 10.0 (3.0, 18.3) years, P = 0.002). TIR was higher in the individuals with preserved C-peptide than those with decreased C-peptide (67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P < 0.001), and time above range was significantly lower in those with preserved C-peptide (28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P < 0.001). Preserved C-peptide was associated with lower glucose variability, as defined by s.d. (3.0 mmol/L (2.6, 3.4) vs 3.8 mmol/L (3.2, 4.3), P < 0.001) and interquartile range (4.3 mmol/L (3.1, 4.8) vs 5.3 mmol/L (4.5, 6.3), P < 0.001). Metrics related to hypoglycemia were not different between the two groups. Preserved C-peptide secretion was associated with higher TIR and lower glucose variability in Chinese type 1 diabetes adults.

Factors associated with high glucose variability in patients with type 1 diabetes

BACKGROUND: High glucose variability (GV) is recognized as a risk factor for vascular diabetic complications and hypoglycemia. Factors affecting GV in patients with diabetes needed to be clarified.AIM: To determine the factors associated with high GV in adult patients with type 1 diabetes.MATERIALS AND METHODS: We conducted a single center cross-sectional observational study. In-patients with type 1 diabetes aged 18 to 65 years on basal bolus insulin therapy were included. Day-time and nocturnal Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), Mean Absolute Glucose (MAG) were calculated from continuous glucose monitoring data. The values of CV, MAGE, MAG within the upper quartile were considered high.RESULTS: The study included 400 individuals, including 111 on continuous subcutaneous insulin infusion (CSII). Patients with high GV had lower fasting and postprandial C-peptide levels and higher insulin doses. According to ROC analysis, daily insulin dose &gt;0.69 U/kg and estimated glomerular filtration rate (eGFR) ≥90.5 ml/min×1.73 m2 were associated with high nocturnal CV values. Dose of basal insulin &gt;0.292 U/kg and bolus insulin &gt;0.325 U/day were associated with nocturnal MAGE. Body mass index (BMI) ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, HbA1c ≥8.3%, eGFR ≥89.5 ml/ min×1.73m2 increased risk of high MAG at night. High day-time CV values were associated with daily insulin dose ≥0.675 U/kg and daily dose of BI ≥0.286 U/kg. The risk of high MAGE was increased with HbA1c ≥8.24% and basal insulin dose ≥0.286 U/kg. BMI ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, daily dose of bolus and basal insulin ≥0.325 and ≥0.29 U/kg respectively, and HbA1c ≥8.33% were the risk factors for high day-time MAG. Patients on CSII had lower MAGE (p&lt;0.001) and MAG (p=0.008) compared to those on multiple daily injections.CONCLUSION: In type 1 diabetes, high GV is associated with undetectable residual insulin secretion, normal or reduced body weight, preserved kidney function, supraphysiological doses of insulin, and non-target HbA1c. Patients on CSII have a lower GV than those on multiple daily injections.

Compensatory thalamocortical functional hyperconnectivity in type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with brain damage and cognitive decline. Despite the fact that the thalamus involves aspects of cognition and is typically affected in T2DM, existing knowledge of subregion-level thalamic damage and its associations with cognitive performance in T2DM patients is limited. The thalamus was subdivided into 8 subregions in each hemisphere. Resting-state functional and structural MRI data were collected to calculate resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each thalamic subregion in 62 T2DM patients and 50 healthy controls. Compared with controls, T2DM patients showed increased rsFC of the medial pre-frontal thalamus, posterior parietal thalamus, and occipital thalamus with multiple cortical regions. Moreover, these thalamic functional hyperconnectivity were associated with better cognitive performance and lower glucose variability in T2DM patients. However, there were no group differences in GMV for any thalamic subregions. These findings suggest a possible neural compensation mechanism whereby selective thalamocortical functional hyperconnectivity facilitated by better glycemic control help to preserve cognitive ability in T2DM patients, which may ultimately inform intervention and prevention of T2DM-related cognitive decline in real-world clinical settings.

157-LB: Scanning Frequency and Glucose Variability in the First Trimester of T1DM Pregnancies Predict Time Spent in Very Low Glucose Range in the Last One—Analysis of Intermittently Scanned Continuous Glucose Monitoring

Scanning frequency and glucose variability in the first trimester of T1DM pregnancies predict time spent in very low glucose range in the last one: analysis of intermittently scanned continuous glucose monitoring Hypoglycemia is inevitable side effect of tight glycemic control in type 1 diabetes mellitus (T1DM) pregnancies. Using technology novel risk factors are revealed. Total of 34 patients (mean age 29.8 ± 6.1 yrs, BMI 23.6± 3.6 kg/m2, disease duration 15.2± 8.9 yrs) having very low glycemia in third trimester (&amp;lt; 3 mmol/L or 55 mg/dL) were included in the study. Patients used intermittently scanned continuous glucose monitoring (isCGM) FreeStyle Libre, Abott for a minimum of 3 months before conception and had glucose data availability &amp;gt; 80% of the time. Data from first trimester showed mean scanning frequency 12.17 ± 6.5 scans/day, estimated average glucose 7.2 ± 1.4 mmol/L, CV% 41.9 ± 6.5, GMI 6.4 ± 0.5, time below range &amp;lt;3.5 mmol/L or 64 mg/dL 10.7 ± 8.0 % and time spent in very low glucose range &amp;lt;3mmol/L or 55 mg/dL 5.4 ± 4.9 %. In last trimester mean scanning frequency was 16.3 ± 7.6 scans/day, estimated average glucose 6.1 ± 0.9 mmol/L, CV% 34.6 ±6.0 , GMI 5.9 ± 0.4 , time below range 11.0 ±9.3 %, time spent in very low glucose range 5.2 ± 4.8 %. Parameters from the first trimester of pregnancy significantly correlating with time spent in very low glucose range in the third trimester were scanning frequency (r −0.365, p 0.37) and CV % (r 0.465, p 0.006) . Linear regression analysis performed for CV% and scanning frequency showed R square 0.434 and p 0.002 in ANOVA. Two isCGM parameters from first trimester of pregnancy that influence on very low glucose rate in the third one are low scanning frequency and higher %CV. Combined they add to 43% of very low glucose occurrence. Patients who scan frequently in the first trimester of pregnancy and have low glucose variability spend less time in very low glucose range in the third trimester. For the others continuous glucose monitoring with hypo alerts should be offered. Disclosure M. Baretic: None. G. Leksic: None. M. Ivanisevic: None.

Frequency of flash glucose monitoring and glucose metrics: real-world observational data from Saudi Arabia

BackgroundThis real-world data study analyzed glucose metrics from FreeStyle Libre® flash glucose monitoring in relation to scanning frequency, time in range (TIR) and estimated A1c (eA1c) in Saudi Arabia.MethodsAnonymized reader data were analyzed according to scanning frequency quartiles, eA1c categories (<7%,≥7%‒≤9% or>9%) and TIR categories (<50%,≥50%‒≤70% or>70%). Sensors, grouped by reader, were required to have≥120 h of operation. Differences in scanning frequency, eA1c, TIR, time in hypoglycemia and hyperglycemia, and glucose variability (standard deviation [SD] and coefficient of variation [CV]) were analyzed between groups.Results6097 readers, 35,747 sensors, and 40 million automatic glucose measurements were analyzed. Patients in the highest scanning frequency quartile (Q4, mean 32.0 scans/day) had lower eA1c (8.47%), greater TIR (46.4%) and lower glucose variation (SD 75.0 mg/dL, CV 38.2%) compared to the lowest quartile (Q1, mean 5.2 scans/day; eA1c 9.77%, TIR 32.8%, SD 94.9 mg/dL, CV 41.3%). Lower eA1c and higher TIR were associated with greater scanning frequency, lower glucose variability and less time in hyperglycemia.ConclusionsHigher scanning frequency in flash glucose users from Saudi Arabia is associated with lower eA1c, higher TIR, lower glucose variability and less time in hypoglycemia or hyperglycemia.

Glucose variability is associated with an adverse vascular profile but only in the presence of insulin resistance in individuals with type 1 diabetes: An observational study.

Aims/HypothesisWe hypothesised that the detrimental effect of high glucose variability (GV) in people with type 1 diabetes is mainly evident in those with concomitant insulin resistance.MethodsWe conducted secondary analyses on continuous glucose monitoring (CGM) using baseline observational data from three randomised controlled trials and assessed the relationship with established vascular markers. We used standard CGM summary statistics and principal component analysis to generate individual glucose variability signatures for each participant. Cluster analysis was then employed to establish three GV clusters (low, intermediate, or high GV, respectively). The relationship with thrombotic biomarkers was then investigated according to insulin resistance, assessed as estimated glucose disposal rate (eGDR).ResultsOf 107 patients, 45%, 37%, and 18% of patients were assigned into low, intermediate, and high GV clusters, respectively. Thrombosis biomarkers (including fibrinogen, plasminogen activator inhibitor-1, tissue factor activity, and tumour necrosis factor-alpha) increased in a stepwise fashion across all three GV clusters; this increase in thrombosis markers was evident in the presence of low but not high eGDR and at a threshold of eGDR <5.1 mg/kg/min.ConclusionHigher GV is associated with increased thrombotic biomarkers in type 1 diabetes but only in those with concomitant insulin resistance.

Predictive low-glucose suspend system and glycemic variability

Predictive low-glucose suspend system and glycemic variability

Sexual dysfunctions and short-term glucose variability in young men with type 1 diabetes

PurposeErectile dysfunction (ED) and premature ejaculation (PE) are common sexual disorders in people with diabetes. Glucose variability (GV) has been recognized as a predictor of microvascular complications. The aim of this study was to investigate the relationship between glucose variability and sexual dysfunctions in young men with type 1 diabetes.MethodsOne hundred and twelve patients with type 1 diabetes, aged 18–30 years, were enrolled. Patients were divided into two groups according to glucose variability [group 1 (high GV with coefficient of variation ≥ 36%)] and group 2 (low GV with coefficient of variation < 36%)). The presence of sexual dysfunctions was investigated with validated questionnaires.ResultsED and PE prevalence rates in group 1 were 26% and 13%, respectively. Similarly, in group 2, the prevalence of ED was 24%, and the prevalence of PE was 13%. In both groups, no significant associations between sexual dysfunctions and parameters of glucose variability were found. Multiple regression analysis identified age and depression as independent predictors of ED and PE.ConclusionYoung male patients affected by type 1 diabetes with high or low glucose variability show a similar prevalence of sexual dysfunctions. ED is the most common sexual dysfunction in diabetic men. Age and depression were the only independent predictive factors for sexual dysfunctions in this population.

Pancreatic β-Cell Function Is Associated with Augmented Counterregulation to In-Exercise Hypoglycemia in Type 1 Diabetes.

This study aimed to investigate the influence of residual β-cell function on counterregulatory hormonal responses to hypoglycemia during acute physical exercise in people with type 1 diabetes (T1D). A secondary aim was to explore relationships between biomarkers of pancreatic β-cell function and indices of glycemia following acute exercise including the nocturnal period. This study involved an exploratory, secondary analysis of data from individuals with T1D who partook in a four-peroid, randomized, cross-over trial involving a bout of evening exercise followed by an overnight stay in a clinical laboratory facility. Participants were split into two groups: (i) a stimulated C-peptide level of ≥30 pmol⋅L-1 (low-level secretors [LLS], n = 6) or (ii) <30 pmol⋅L-1 (microsecretors [MS], n = 10). Pancreatic hormones (C-peptide, proinsulin, and glucagon), catecholamines (epinephrine [EPI] and norepinephrine [NE]), and metabolic biomarkers (blood glucose, blood lactate, and β-hydroxybutyrate) were measured at rest, during exercise with and without a hypoglycemic (blood glucose ≤3.9 mmol⋅L-1) episode, and throughout a 13-h postexercise period. Interstitial glucose monitoring was used to assess indices of glycemic variability. During in-exercise hypoglycemia, LLS presented with greater sympathoadrenal (EPI and NE P ≤ 0.05) and ketone (P < 0.01) concentrations. Glucagon remained similar (P = 0.09). Over exercise, LLS experienced larger drops in C-peptide and proinsulin (both P < 0.01) as well as greater increases in EPI (P < 0.01) and β-hydroxybutyrate (P = 0.03). LLS spent less time in the interstitial-derived hypoglycemic range acutely postexercise and had lower glucose variability throughout the nocturnal period. Higher residual β-cell function was associated with greater sympathoadrenal and ketonic responses to exercise-induced hypoglycemia as well as improved glycemia leading into and throughout the nocturnal hours. Even a minimal amount of residual β-cell function confers a beneficial effect on glycemic outcomes during and after exercise in people with T1D.

Continuous Glucose Monitoring in Adults with Type 1 Diabetes: Real-World Data from the German/Austrian Prospective Diabetes Follow-Up Registry.

Background: To analyze key indicators of metabolic control in adults with type 1 diabetes (T1D) using real-time or intermittent scanning continuous glucose monitoring (rtCGM/iscCGM) during real-life care, based on the German/Austrian/Swiss Prospective Diabetes Follow-up (DPV) registry. Methods: Cross-sectional analysis including 233 adults with T1D using CGM. We assessed CGM metrics by gender, age group (18 to <30 years vs. ≥30 years), insulin delivery method (multiple daily injections vs. continuous subcutaneous insulin infusion [CSII]) and sensor type (iscCGM vs. rtCGM), working days versus weekends, and daytime versus night-time using multivariable linear regression models (adjusted for demographic variables) or Wilcoxon signed-rank test. Results: Overall, 79/21% of T1D patients used iscCGM/rtCGM. Those aged ≥30 years spent more time in range (TIR [70-180 mg/dL] 54% vs. 49%) and hypoglycemic range <70 mg/dL (7% vs. 5%), less time in hyperglycemic range >180 mg/dL (38% vs. 46%) and had a lower glucose variability (coefficient of variation [CV] 36% vs. 37%) compared with adults aged <30 years. We found no significant differences between genders. Multivariable regression models revealed the highest Time In Range (TIR) and lowest time with sensor glucose >250 mg/dL, CV and daytime-night-time differences in those treated with CSII and rtCGM. Glucose profiles were slightly more favorable on working days. Conclusions: In our real-world data, rtCGM versus iscCGM was associated with a higher percentage of TIR and improved metabolic stability. Differences in ambulatory glucose profiles on working and weekend days may indicate lifestyle habits affecting glycemic stability. Real-life CGM results should be included in benchmarking reports in addition to hemoglobin A1c (HbA1c) and history of hypoglycemia.