To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.
...Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial.
Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey.
Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function.
One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%.
ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes.
- ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes is an established risk factor for heart failure, but because nearly all heart failure occurs in older individuals, the excess risk and risk factors for heart failure in individuals with type ...1 diabetes are not known. We aimed to determine the excess risk of heart failure in individuals with type 1 diabetes overall and by different levels of glycaemic control and albuminuria.
In this prospective case-control study, we identified all individuals with type 1 diabetes registered in the Swedish National Diabetes Registry between Jan 1, 1998, and Dec 31, 2011, and five controls randomly selected from the general population for each patient, matched according to age, sex, and county, and compared them with respect to subsequent hospital admissions for heart failure, with hazard ratios calculated with Cox regression.
In a cohort of 33 402 patients (mean age at baseline 35 years SD 14, 15 058 45% women, and mean duration of diabetes 20·1 years SD 14·5), over a mean follow-up of 7·9 years, 1062 (3%) patients were admitted to hospital with a diagnosis of heart failure, compared with 1325 (1%) of 166 228 matched controls over 8·3 years, giving a HR 4·69 (95% CI 3·64-6·04), after adjustment for time-updated age, sex, time-updated diabetes duration, birth in Sweden, educational level, and baseline comorbidities. Worse glycaemic control was associated with increased risk of heart failure in a graded fashion, and so was the presence of albuminuria. Risk of heart failure was also increased among those with well controlled diabetes (adjusted HR 2·16 95% CI 1·55-3·01) and in those with no albuminuria (3·38 2·51-4·57), but not in the subgroup both well-controlled and with normoalbuminuria (1·59 0·70-3·58).
Individuals with type 1 diabetes had a four-times increase in the risk of being admitted to hospital with heart failure compared with population-based controls. Poor glycaemic control and impaired renal function substantially increased the risk of heart failure.
The Swedish state, Swedish Society for Physicians, the Health & Medical Care Committee of the Regional Executive Board (Region Vastra Gotaland, Sweden), the Swedish Heart-Lung Foundation, Diabetes Wellness, Novo Nordisk Foundation (PI M Lind), the Swedish Research Council, and the Swedish Council for working life and social research (Epilife).
We sought to examine in individuals with SARS-CoV-2 infection whether risk for thrombotic and thromboembolic events (TTE) is modified by presence of a diabetes diagnosis. Furthermore, we analysed ...whether differential risk for TTEs exists in type 1 diabetes mellitus (T1DM) versus type 2 diabetes mellitus (T2DM).
Retrospective case-control study.
The December 2020 version of the
COVID-19 database is a deidentified, nationwide database containing electronic medical record (EMR) data from 87 US-based health systems.
We analysed EMR data for 322 482 patients >17 years old with suspected or confirmed SARS-CoV-2 infection who received care between December 2019 and mid-September 2020. Of these, 2750 had T1DM; 57 811 had T2DM; and 261 921 did not have diabetes.
TTE, defined as presence of a diagnosis code for myocardial infarction, thrombotic stroke, pulmonary embolism, deep vein thrombosis or other TTE.
Odds of TTE were substantially higher in patients with T1DM (adjusted OR (AOR) 2.23 (1.93-2.59)) and T2DM (AOR 1.52 (1.46-1.58)) versus no diabetes. Among patients with diabetes, odds of TTE were lower in T2DM versus T1DM (AOR 0.84 (0.72-0.98)).
Risk of TTE during COVID-19 illness is substantially higher in patients with diabetes. Further, risk for TTEs is higher in those with T1DM versus T2DM. Confirmation of increased diabetes-associated clotting risk in future studies may warrant incorporation of diabetes status into SARS-CoV-2 infection treatment algorithms.
To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in ...individuals with elevated risk for diabetes.
We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.
Follow-up of clinical trial.
504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.
Relative risk of CVD.
Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.
Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diet is an important factor in managing glycemic control in type 1 diabetes (T1D). Reducing carbohydrate intake may be important for stabilizing blood glucose levels in certain groups of patients ...with T1D. There are few studies examining the effects of a low carbohydrate diet in patients with T1D. The aim of this study is to investigate the effects of carbohydrate intake on glucose control in adults with T1D.
Adults with T1D (
= 54) and inadequate glycemic control (HbA1c ≥ 7.5%; 58 mmol/mol) were randomized in a cross-over design to a moderate carbohydrate diet (30 percent of total energy from carbohydrates) versus a traditional diabetes diet (50 percent of total energy from carbohydrates) for 4 weeks with a between wash-out period of 4 weeks. Masked continuous glucose monitoring was used throughout the study to evaluate effects on mean blood glucose levels, time-in-range, hypoglycemia, hyperglycemia, and glycemic variability. Diabetes treatment satisfaction, hypoglycemic confidence, and physical activity were measured using questionnaires during different phases of the trial. HbA1c, blood lipids, blood pressure, and ketone levels were also measured. The primary endpoint is the difference in mean blood glucose level between the diet periods. Study completion is anticipated during winter 2022.
The study seeks to increase knowledge about the effects of dietary carbohydrate intake on glycemic control and other health parameters in patients with T1D. If beneficial effects on mean blood glucose level without elevated risk of hypoglycemia or ketoacidosis are shown, a moderate carbohydrate diet may be a treatment option for people with T1D that have unsatisfactory blood glucose levels.
www.clinicaltrials.gov, ID: NCT03400618.
IntroductionType 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved ...therapy exists to halt this detrimental immunologic process. In a recent phase 2b study, intralymphatic administration of recombinant human glutamic acid decarboxylase 65 kDa (rhGAD65) adsorbed to Alhydrogel adjuvant to individuals recently diagnosed with T1D and carrying the HLA DR3-DQ2 haplotype showed promising results in preserving endogenous insulin secretion, confirming the results of a large meta-analysis of three randomised placebo-controlled trials of subcutaneous rhGAD65. The aim of the current precision medicine phase 3 study is to determine whether intralymphatic administration of rhGAD65 preserves insulin secretion and improves glycaemic control in presumed responder individuals with recently diagnosed T1D carrying HLA DR3-DQ2.Methods and analysisIndividuals ≥12 and <29 years recently diagnosed with T1D (<6 months) will be screened for the HLA DR3-DQ2 haplotype, endogenous insulin production estimated by fasting C-peptide and presence of GAD65 antibodies. 330 patients are planned to be randomised to 3 monthly intralymphatic injections of rhGAD65 or placebo (both accompanied by oral vitamin D supplementation), followed by 22 months of follow-up. The study is powered to detect a treatment effect in the two coprimary endpoints; change from baseline in AUC(0-120min) C-peptide levels during a mixed meal tolerance test, and change from baseline in glycaemic control estimated by haemoglobin A1c at 24 months. Secondary endpoints include effects on glucose patterns collected by masked continuous glucose monitoring, proportion of patients in partial remission and number of episodes of severe hypoglycaemia and/or diabetic ketoacidosis.Ethics and disseminationThe trial is approved by Ethics Committees in Poland (124/2021), the Netherlands (R21.089), Sweden (2021-05063), Czech Republic (EK-1144/21), Germany (2021361) and Spain (21/2021). Results will be published in international peer-reviewed scientific journals and presented at national and international conferences.Trial registration numberEudraCT identifier: 2021-002731-32, NCT identifier: NCT05018585.
To investigate early and long-term outcomes after treatment of carotid artery stenosis in patients with type 2 diabetes (T2D) compared to patients without T2D.
This observational nationwide ...population-based retrospective cohort study investigated all T2D patients treated for carotid stenosis registered in the National Swedish Vascular Surgery and the National Diabetes Registries. Data was collected prospectively for all patients after carotid intervention, during 2009-2015. We estimated crude early (within 30-days) hazard ratios (HRs) risk of stroke and death, and long-term HRs risk, adjusted for confounders with 95% confidence intervals (CIs), for stroke and death and major adverse cardiovascular events (MACE) by using inverse probability of treatment weighting matching.
A total of 1341 patients with T2D and 4162 patients without T2D were included; 89% treated for symptomatic carotid stenosis, 96% with carotid endarterectomy. There was an increased early risk, HRs (95% CI), for stroke in T2D patients 1.65 (1.17-2.32), whereas risk for early death 1.00 (0.49-2.04) was similar in both groups. During a median follow-up of 4.3 (T2D) and 4.6 (without T2D), with a maximum of 8.0 years; after propensity score matching there was an increased HRs (95% CI) of stroke 1.27 (1.05-1.54) and death 1.27 (1.10-1.47) in T2D patients compared to patients without T2D. Corresponding numbers for MACE were 1.21 (1.08-1.35).
Patients with T2D run an increased risk for stroke, death, and MACE after carotid intervention. They also have an increased perioperative risk for stroke, but not for death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The updated mean HbA1c has been used in risk estimates of diabetic complications, but it does not take into account the temporal relationship between HbA1c and diabetic complications. We studied ...whether the updated mean HbA1c underestimated the risk of diabetic complications.
Continuous HbA1c curves for 10,000 hypothetical diabetes patients were simulated over an average of 7 years. Simulations were based on HbA1c values encountered in clinical practice. We assumed that each short time interval of the continuous HbA1c curves had a long-lasting effect on diabetic complications, as evidenced by earlier studies. We tested several different HbA1c variables including various profiles, e.g. different duration, of such a long-lasting effect. The predictive power of these variables was compared with that of the updated mean HbA1c.
The predictive power of the constructed HbA1c variables differed considerably compared to that of the updated mean HbA1c. The risk increase per standard deviation could be almost 100% higher for a constructed predictor than the updated mean HbA1c.
The importance of good glycemic control in preventing diabetic complications could have been underestimated in earlier hallmark studies by not taking the time-dependent effect of HbA1c into account.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Body mass index (BMI) may be a stronger risk factor for heart failure than for coronary heart disease in type 2 diabetes mellitus, but prior studies have not been powered to investigate ...the relative and absolute risks for acute myocardial infarction and heart failure in type 2 diabetes mellitus by BMI and glycemic level combined as compared with age- and sex-matched general population comparators. Methods and Results We identified 181 045 patients from The Swedish National Diabetes Registry, registered during 1998 to 2012 and 1538 434 general population comparators without diabetes mellitus, matched for age, sex, and county, all without prior major cardiovascular disease. Cases and comparators were followed with respect to the outcomes through linkage to the Swedish Inpatient Registry. Over a median follow-up time of 5.7 years, there were 28 855 acute myocardial infarction and 33 060 heart failure cases among patients and comparators. Excess risk (above that of comparators in whom no data on hemoglobin A1c and BMI was available), incidence rates and hazard ratios for heart failure were substantially higher among the obese patients compared with those with low BMI, where very obese patients (BMI ≥40 kg/m
) who also had poor glycemic control, suffered a 7-fold risk of heart failure versus comparators (reference level). By contrast, for acute myocardial infarction, the highest absolute and relative risks were found among patients with poor glycemic control, with no additional risk conferred by increasing BMI. Conclusions BMI is a strong independent risk factor for heart failure but not for acute myocardial infarction among patients with type 2 diabetes mellitus.
BackgroundHistorically, the incidence of cardiovascular disease and mortality in persons with Type 1 diabetes (T1D) has been increased compared to the general population. Contemporary studies on time ...trends of mortality and cardiovascular disease are sparse. MethodsIn this observational study, T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with T1D overall and when stratified for prevalent cardiovascular and renal disease relative to controls. FindingsMean age in persons with T1D was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex- adjusted mortality rates declined over time in both groups but remained significantly higher in those with T1D compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8·08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4-5.0 times from 2017 to 2019 in those with T1D. T1D persons ≥45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. InterpretationExcess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to close the gap in mortality for individuals with T1D. FundingThis study was financed by grants from the ALF-agreement, NovoNordisk Foundation and the Swedish Heart and Lung Foundation.
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