scholarly journals Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial

2021 ◽  
Author(s):  
Xiuzhen Zhang ◽  
Dan Xu ◽  
Ping Xu ◽  
Shufen Yang ◽  
Qingmei Zhang ◽  
...  

Introduction: Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM. Objectives: In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored. Patients and methods: A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000- 2000 mg metformin daily add-on insulin (MET group, n=34) or insulin (Non-MET group, n=31). After, baseline measurements were repeated. Results: The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with Non-MET group [-1.58 (-3.35,0.31) mmol/L versus 1.36 (-1.12,2.24) mmol/L, P=0.004]. In parallel, the largest amplitude of glycemic excursions [-2.83 (-5.47,-0.06) mmol/L versus 0.45 (-1.29,4.48) mmol/L, P=0.004], the standard deviation of blood glucose [-0.85 (-1.51,0.01) mmol/L versus -0.14 (-0.68,1.21) mmol/L, P=0.015], and the coefficient of variation [-6.66 (-15.00,1.50) % versus -1.60 (-6.28,11.71) %, P=0.012] all demonstrated improvement in the MET group, compared with the Non-MET group. Significant reduction in insulin dose, body mass index and body weight were observed in patients in MET, not those in Non-MET group. Conclusion: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Author(s):  
XIUZHEN zhang ◽  
Dan Xu ◽  
ping xu ◽  
Shufen Yang ◽  
Qingmei Zhang ◽  
...  

Introduction: Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes(T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM. Objectives: In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored. Patients and methods: A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000- 2000 mg metformin daily add-on insulin (MET+INS, n=34) or insulin (INS, n=31). After, baseline measurements were repeated. Results: The mean amplitude of glycemic excursions was substantially reduced in the MET+INS group, compared with the INS group (-1.47±3.39 mmol/L versus 1.05±4.24 mmol/L, P=0.012). In parallel, the largest amplitude of glycemic excursions (-2.28±4.71 mmol/L versus 1.77±5.71 mmol/L, P=0.003), the standard deviation of blood glucose (- 0.62±1.15 mmol/L versus 0.08±1.23 mmol/L, P=0.023), and the coefficient of variation (-6.08±12.31 % versus 2.29±11.57 %, P=0.008) all demonstrated improvement in the MET+INS group, compared with the INS group. Significant reduction in the insulin dose, body mass index and body weight were observed in patients with MET+INS, not those with INS. Conclusion: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ziyang Shen ◽  
Hemin Jiang ◽  
Rong Huang ◽  
Yunting Zhou ◽  
Qian Li ◽  
...  

AbstractPrevious studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM.


Author(s):  
Emine Ayça Cimbek ◽  
Aydın Bozkır ◽  
Deniz Usta ◽  
Nazım Ercüment Beyhun ◽  
Ayşenur Ökten ◽  
...  

Abstract Objectives Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR. Methods This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of ≤9. Results Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3 ± 0.12 vs. 7.23 ± 0.15, p=0.003), higher C-peptide levels (0.45 ± 0.31 ng/mL vs. 0.3 ± 0.22, p=0.003), and they were significantly older (9.3 ± 3.6 years vs. 7.3 ± 4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23 ± 0.14 vs. 0.4 ± 0.17 U/kg/day, p=0.014). Conclusions Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients.


2020 ◽  
pp. 193229682092225
Author(s):  
Morten Hasselstrøm Jensen ◽  
Simon Lebech Cichosz ◽  
Irl B. Hirsch ◽  
Peter Vestergaard ◽  
Ole Hejlesen ◽  
...  

Background: The prevalence of smoking and diabetes is increasing in many developing countries. The aim of this study was to investigate the association of smoking with inadequate glycemic control and glycemic variability with continuous glucose monitoring (CGM) data in people with type 1 diabetes. Methods: Forty-nine smokers and 320 nonsmokers were obtained from the Novo Nordisk Onset 5 trial. After 16 weeks of treatment with continuous subcutaneous insulin infusion, risk of not achieving glycemic target and glycemic variability from six CGM measures was investigated. Analyzes were carried out with logistic regression models (glycemic target) and general linear models (glycemic variability). Finally, CGM median profiles were examined for the identification of daily glucose excursions. Results: A 4.7-fold (95% confidence interval: 1.5-15.4) increased risk of not achieving glycemic target was observed for smokers compared with nonsmokers. Increased time in hyperglycemia, decreased time in range, increased time in hypoglycemia (very low interstitial glucose), and increased fluctuation were observed for smokers compared with nonsmokers from CGM measures. CGM measures of coefficient of variation and time in hypoglycemia were not statistically significantly different. Examination of CGM median profiles revealed that risk of morning hypoglycemia is increased for smokers. Conclusions: In conclusion, smoking is associated with inadequate glycemic control and increased glycemic variability for people with type 1 diabetes with especially risk of morning hypoglycemia. It is important for clinicians to know that if the patient has type 1 diabetes and is smoking, a preemptive action to treat high glycated hemoglobin levels should not necessarily be treatment intensification due to the risk of hypoglycemia.


2011 ◽  
Vol 165 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Ajay Varanasi ◽  
Natalie Bellini ◽  
Deepti Rawal ◽  
Mehul Vora ◽  
Antoine Makdissi ◽  
...  

ObjectiveTo determine whether the addition of liraglutide to insulin to treat patients with type 1 diabetes leads to an improvement in glycemic control and diminish glycemic variability.Subjects and methodsIn this study, 14 patients with well-controlled type 1 diabetes on continuous glucose monitoring and intensive insulin therapy were treated with liraglutide for 1 week. Of the 14 patients, eight continued therapy for 24 weeks.ResultsIn all the 14 patients, mean fasting and mean weekly glucose concentrations significantly decreased after 1 week from 130±10 to 110±8 mg/dl (P<0.01) and from 137.5±20 to 115±12 mg/dl (P<0.01) respectively. Glycemic excursions significantly improved at 1 week. The mean s.d. of glucose concentrations decreased from 56±10 to 26±6 mg/dl (P<0.01) and the coefficient of variation decreased from 39.6±10 to 22.6±7 (P<0.01). There was a concomitant fall in the basal insulin from 24.5±6 to 16.5±6 units (P<0.01) and bolus insulin from 22.5±4 to 15.5±4 units (P<0.01).In patients who continued therapy with liraglutide for 24 weeks, mean fasting, mean weekly glucose concentrations, glycemic excursions, and basal and bolus insulin dose also significantly decreased (P<0.01). HbA1c decreased significantly at 24 weeks from 6.5 to 6.1% (P=0.02), as did the body weight by 4.5±1.5 kg (P=0.02).ConclusionLiraglutide treatment provides an additional strategy for improving glycemic control in type 1 diabetes. It also leads to weight loss.


2021 ◽  
Vol 14 ◽  
pp. 117955142110405
Author(s):  
Masahide Hamaguchi ◽  
Yoshitaka Hashimoto ◽  
Toru Tanaka ◽  
Goji Hasegawa ◽  
Michiyo Ishii ◽  
...  

Background: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. Methods: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Alexandra Bodan

Research shows women with type 1 diabetes (T1D) face a disproportionately increased risk for development of cardiovascular disease (CVD) compared to men. We posit, adolescence may be a critical time period for CVD risk development. Our study examined the effects on gender differences in Hemoglobin A1c (HbA1c) and Body Mass Index z-score (BMIz) across puberty in children with T1D in a large pediatric diabetes specialty clinic. A total of 733 T1D children (M=355, F=378) aged 9-17 with a total of 21,534 visits from the Barbara Davis Center were suitable for this retrospective cohort study. To exam HbA1c and BMIz overtime by gender we used a linear mixed model with SAS version 9.4. HbA1c increased with age in both genders (p<0.0001), but there was a greater increase in girls across adolescence (sex by age interaction, p<0.0007). BMIz increased with age in girls only (sex by age interaction, p<0.0001). Teenagers had worse glycemic control than younger children, and girls had worse glycemic control with greater obesity rates than boys. This gender difference in glycemic control and obesity during puberty may explain the increased CVD risk seen in women with T1D compared to men.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e029859
Author(s):  
Bettina Ewers ◽  
Tina Vilsbøll ◽  
Henrik Ullits Andersen ◽  
Jens Meldgaard Bruun

IntroductionClinical guidelines recommend that patients with type 1 diabetes (T1D) learn carbohydrate counting or similar methods to improve glycaemic control. Although systematic educating in carbohydrate counting is still not offered as standard-of-care for all patients on multiple daily injections (MDI) insulin therapy in outpatient diabetes clinics in Denmark. This may be due to the lack of evidence as to which educational methods are the most effective for training patients in carbohydrate counting. The objective of this study is to compare the effect of two different educational programmes in carbohydrate counting with the usual dietary care on glycaemic control in patients with T1D.Methods and analysisThe study is designed as a randomised controlled trial with a parallel-group design. The total study duration is 12 months with data collection at baseline, 6 and 12 months. We plan to include 231 Danish adult patients with T1D. Participants will be randomised to one of three dietician-led interventions: (1) a programme in basic carbohydrate counting, (2) a programme in advanced carbohydrate counting including an automated bolus calculator or (3) usual dietary care. The primary outcome is changes in glycated haemoglobin A1c or mean amplitude of glycaemic excursions from baseline to end of the intervention period (week 24) between and within each of the three study groups. Other outcome measures include changes in other parameters of plasma glucose variability (eg, time in range), body weight and composition, lipid profile, blood pressure, mathematical literacy skills, carbohydrate estimation accuracy, dietary intake, diet-related quality of life, perceived competencies in dietary management of diabetes and perceptions of an autonomy supportive dietician-led climate, physical activity and urinary biomarkers.Ethics and disseminationThe protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.gov Registry (NCT03623113).


2021 ◽  
Vol 14 ◽  
pp. 117955142110137
Author(s):  
Bader Alzahrani ◽  
Saad Alzahrani ◽  
Mussa H Almalki ◽  
Souha S Elabd ◽  
Shawana Abdulhamid Khan ◽  
...  

Background: Glucose variability (GV) is a common and challenging clinical entity in the management of people with type 1 diabetes (T1DM). The magnitude of GV in Saudi people with T1DM was not addressed before. Therefore, we aimed to study GV in a consecutive cohort of Saudis with T1DM. Methods: We prospectively assessed interstitial glucose using FreeStyle® Libre flash glucose monitoring in people with TIDM who attended follow-up in the diabetes clinics at King Fahad Medical City between March and June 2017. Glycemia profile, standard deviation (SD), coefficient of variation (CV), mean of daily differences (MODD), and mean amplitude of glucose excursion (MAGE) were measured using the standard equations over a period of 2 weeks. Results: Fifty T1DM subjects (20 males) with mean age 20.2 ± 6.1 years and mean fortnight glucose 192 ± 42.3 mg/dl were included. The mean SD of 2-week glucose readings was 100.4 ± 36.3 mg/dl and CV was 52.1% ± 13%. Higher levels of glucose excursions were also observed. MODD and MAGE were recorded as 104.5 ± 51.7 and 189 ± 54.9 mg/dl, respectively which is 2 to 4 times higher than the international standards. Higher MODD and MAGE were observed on weekends compared to weekdays (111.3 ± 62.1 vs 98.6 ± 56.2 mg/dl and 196.4 ± 64.6 vs 181.7 ± 52.4 mg/dl, respectively; P ⩽ .001). Conclusion: Higher degree of glycemic variability was observed in this cohort of TIDM Saudis. Weekends were associated with higher glucose swings than weekdays. More studies are needed to explore these findings further.


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