The dawn phenomenon in type 2 diabetes: its association with glucose excursions and changes after oral glucose-lowering drugs.
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ABSTRACT: Background
We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D).Methods
We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level.Results
A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074-0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7-28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6-34.6 ± 17.0 mg/dl, p = 0.776).Conclusion
Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.
SUBMITTER: Wang JS
PROVIDER: S-EPMC8361546 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLifetime glycemic exposure and its relationship with age at diagnosis in type 2 diabetes (T2D) are unknown. Pharmacologic glycemic management strategies for young-onset T2D (age at diagnosis <40 years) are poorly defined. We studied how age at diagnosis affects glycemic exposure, glycemic deterioration, and responses to oral glucose-lowering drugs (OGLDs).Methods and findingsIn a population-based cohort (n = 328,199; 47.2% women; mean age 34.6 and 59.3 years, respectively, for young-onset and usual-onset [age at diagnosis ≥40 years] T2D; 2002-2016), we used linear mixed-effects models to estimate the association between age at diagnosis and A1C slope (glycemic deterioration) and tested for an interaction between age at diagnosis and responses to various combinations of OGLDs during the first decade after diagnosis. In a register-based cohort (n = 21,016; 47.1% women; mean age 43.8 and 58.9 years, respectively, for young- and usual-onset T2D; 2000-2015), we estimated the glycemic exposure from diagnosis until age 75 years. People with young-onset T2D had a higher mean A1C (8.0% [standard deviation 0.15%]) versus usual-onset T2D (7.6% [0.03%]) throughout the life span (p < 0.001). The cumulative glycemic exposure was >3 times higher for young-onset versus usual-onset T2D (41.0 [95% confidence interval 39.1-42.8] versus 12.1 [11.8-12.3] A1C-years [1 A1C-year = 1 year with 8% average A1C]). Younger age at diagnosis was associated with faster glycemic deterioration (A1C slope over time +0.08% [0.078-0.084%] per year for age at diagnosis 20 years versus +0.02% [0.016-0.018%] per year for age at diagnosis 50 years; p-value for interaction <0.001). Age at diagnosis ≥60 years was associated with glycemic improvement (-0.004% [-0.005 to -0.004%] and -0.02% [-0.027 to -0.0244%] per year for ages 60 and 70 years at diagnosis, respectively; p-value for interaction <0.001). Responses to OGLDs differed by age at diagnosis (p-value for interaction <0.001). Those with young-onset T2D had smaller A1C decrements for metformin-based combinations versus usual-onset T2D (metformin alone: young-onset -0.15% [-0.105 to -0.080%], usual-onset -0.17% [-0.179 to -0.169%]; metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitor: young-onset -0.44% [-0.476 to -0.405%], usual-onset -0.48% [-0.498 to -0.459%]; metformin and α-glucosidase inhibitor: young-onset -0.40% [-0.660 to -0.144%], usual-onset -0.25% [-0.420 to -0.077%]) but greater responses to other combinations containing sulfonylureas (sulfonylurea alone: young-onset -0.08% [-0.099 to -0.065%], usual-onset +0.06% [+0.059 to +0.072%]; sulfonylurea and α-glucosidase inhibitor: young-onset -0.10% [-0.266 to 0.064%], usual-onset: 0.25% [+0.196% to +0.312%]). Limitations include possible residual confounding and unknown generalizability outside Hong Kong.ConclusionsIn this study, we observed excess glycemic exposure and rapid glycemic deterioration in young-onset T2D, indicating that improved treatment strategies are needed in this setting. The differential responses to OGLDs between young- and usual-onset T2D suggest that better disease classification could guide personalized therapy.
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Project description:Background and objectivePrevious experimental studies have shown that fructose interacts with glucose metabolism by increasing hepatic glucose uptake. However, human studies investigating the effects of small ('catalytic') amounts of fructose, added to an oral glucose load, on plasma glucose levels remain inconclusive. The aim of this study, therefore, was to repeat and extend these previous studies by examining the plasma glucose response during a 75 g oral glucose tolerance test (OGTT) with the addition of different doses of fructose.MethodsHealthy adults (n = 13) received an OGTT without addition of fructose and OGTTs with addition of different doses of fructose (1, 2, 5, 7.5 and 15 g) in a random order, on six separate occasions. Plasma glucose levels were measured every 15 min for 120 min during the study.FindingsThe plasma glucose incremental area under the curve (iAUC) of the OGTT without addition of fructose was not significantly different from any OGTT with fructose (p ≥ 0.2 for all fructose doses). Similar results were observed when these data were clustered with data from a similar, previous study (pooled mean difference: 10.6; 95%CI: 45.0; 23.8 for plasma glucose iAUC of the OGTT without addition of fructose versus an OGTT with 5 g fructose; fixed-effect meta-analysis, n = 38). Of interest, serum fructose increased from 4.8 μmol/L (interquartile range: 4.1-5.9) at baseline to 5.3 μmol/L (interquartile range: 4.8-7.5) at T = 60 min during an OGTT without addition of fructose (p = 0.002).ConclusionLow doses of fructose added to an OGTT do not affect plasma glucose levels in healthy adults. The role of endogenous fructose production, as a potential explanation of these null-findings, deserves further investigation.
| S-EPMC10209703 | biostudies-literature
Project description:This study aimed to compare conventional medication management of type 2 diabetes (T2D) to medication management in conjunction with a lifestyle intervention using continuous glucose monitoring to minimize glucose excursions. Thirty adults (63% female; mean age, 53.3 years) who were diagnosed with T2D for less than 11 years (mean, 5.6 years), had glycated A1c (HbA1c) ≥ 7.0% (51 mmol/mol) (mean 8.8%, [73 mmol/mol]), and were not using insulin, were randomly assigned in a 1:2 ratio to routine care (RC) or 4 group sessions of glycemic excursion minimization plus real-time CGM (GEMCGM). Assessments at baseline and 5 months included a physical exam, metabolic and lipid panels, a review of diabetes medications, and psychological questionnaires. For the week following assessments, participants wore a blinded activity monitor and completed 3 days of 24-hour dietary recall. A subgroup also wore a blinded CGM. GEMCGM participants significantly improved HbA1c (from 8.9% to 7.6% [74-60 mmol/mol] compared with 8.8% to 8.7% [73-72 mmol/mol] for RC (P = .03). Additionally, GEMCGM reduced the need for diabetes medication (P = .01), reduced carbohydrate consumption (P = .009), and improved diabetes knowledge (P = .001), quality of life (P = .01) and diabetes distress (P = .02), and trended to more empowerment (P = .05) without increasing dietary fat, lipids, or hypoglycemia. Confirming our prior research, GEMCGM appears to be a safe, effective lifestyle intervention option for adults with suboptimally controlled T2D who do not take insulin.
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Project description:AimsTo examine the lifestyle profile among persons with and without Type 2 diabetes mellitus (DM) and among users of different glucose-lowering drugs.MethodsWe used questionnaire data from a Danish health survey and identified presence of Type 2 DM and use of medications through medical databases. We calculated age- and gender-standardized prevalence ratios (PRs) of lifestyle factors according to Type 2 DM and different glucose-lowering drugs.ResultsOf 21,637 survey participants aged 25-79 years, 680 (3%) had Type 2 DM (median age 63 years) with a median diabetes duration of 5 years. Participants with Type 2 DM had a substantially higher prevalence of obesity (36% vs. 13%, PR: 3.1, 95% confidence interval (CI): 2.8-3.6), yet more reported to eat a very healthy diet (25% vs. 21%, PR: 1.2, 95% CI: 1.0-1.4) and to exercise regularly (67% vs. 53%, PR: 1.3, 95% CI: 1.2-1.4). Also, fewer were current smokers or had high alcohol intake. When compared with metformin users, obesity was substantially less prevalent in users of sulfonylurea (PR: 0.5, 95% CI: 0.4-0-8), and insulin and analogues (PR: 0.4, 95% CI: 0.3-0.7). Tobacco smoking was more prevalent in sulfonylurea users (PR: 1.4, 95% CI: 0.9-2.1) compared with metformin users. We found no material differences in physical exercise, diet or alcohol intake according to type of glucose-lowering drug.ConclusionsType 2 DM patients are substantially more obese than other individuals, but otherwise report to have a healthier lifestyle. Metformin use is strongly associated with obesity, whereas sulfonylurea use tends to be associated with tobacco smoking.
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Project description:The clinical efficacy of continuous subcutaneous insulin infusion (CSII) therapy combined with six classes of oral glucose-lowering drugs (GLDs) (TZDs/metformin/acarbose/GLP-1 receptor agonist/SGLT-2 inhibitor/DPP-4 inhibitor) was evaluated by a network meta-analysis to provide an evidence-based reference in making a clinical decision on CSII combined with drugs in the treatment of type 2 diabetes. Data were retrieved from eight databases: the Chinese Journal Full-Text Database (CNKI), VIP Chinese Science and Technology Periodicals Full-Text Database (VP-CSFD), Wanfang Data Journal Paper Resource (WANFANG), China Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and Web of Science. The retrieval period dated from the library's construction to 27 June 2021. The search was for randomized, controlled trial studies (RCT) on insulin infusion (CSII) combined with oral hypoglycemic drugs (TZDs/metformin/acarbose/GLP-1 receptor agonist/SGLT-2 inhibitor/DPP-4 inhibitor) in the treatment of type 2 diabetes. Quality evaluation and data extraction were performed on the studies included, and network meta-analysis was performed with R4.0.1 software. A total of 56 publications was included in the final network meta-analysis, with a total sample size of 4395. Results based on the network meta-analysis were that CSII combined with a metformin works best on fasting blood glucose (FBG) and 2 h postprandial blood glucose (2hPG) and improves insulin resistance (lower HOMA-IR levels). CSII combined with a DPP-4 inhibitor had the best clinical effect in reducing glycosylated hemoglobin levels. Treatment with CSII combined with a DPP-4 inhibitor was the fastest way to achieve the blood glucose standard. In terms of insulin dosage, an insulin pump (CSII) combined with the GLP-1 receptor agonist can significantly reduce insulin dosage. Network meta-analysis evidence suggests that an insulin infusion (CSII) combined with oral hypoglycemic drugs can improve clinical efficacy in controlling blood sugar and improving insulin resistance, insulin dosage, and standard time. However, the most outstanding performance was that of insulin infusion (CSII) combined with metformin, which had the best clinical effect in controlling blood sugar and improving insulin resistance.
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Project description:AimsType 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death.Methods and resultsPatients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. 'Incident severe COVID-19' was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19.Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA.ConclusionSGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.
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