scholarly journals Risk of atrial fibrillation development of sodium-glucose co-transporter 2 inhibitor and thiazolidinedione treatment among patients with type 2 diabetes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y.R Kim ◽  
S.E Lee ◽  
K.A Kim
Keyword(s):  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Incidence Rates ◽  
Good Choice ◽  
Diabetic Patients ◽  
Funding Sources ◽  
Korean National Health Insurance ◽  
Outcome Event

Abstract Background Type 2 diabetes is an independent risk factor for the development of atrial fibrillation (AF). Recently, SGLT-2i has been shown to decrease the incidence of AF through several mechanisms including reduction of atrial dilatation via diuresis and lowering body weight. On the other hand, the use of TZD was found to protect diabetic patients from new-onset AF in observational studies. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of AF development. Methods Using the Korean National Health Insurance Service database, we included patients with type 2 diabetes who were prescribed SGLT-2i or TZD at least once from January 2014 to December 2018. Patients were followed until the outcome event, death, or 31 December 2018. Sensitivity analysis was performed only including patients who prescribed study drugs ≥90 days. Results A total of 206,986 patients were included (88,227 patients in SGLT-2i group and 118,759 in TZD group). Baseline characteristics were mean age was 57 years and 57.4% were male; mean body mass index was 26.3kg/m2 and 68.3% had hypertension. During follow-up, the incidence rates of AF were 1.36% in SGLT-2i-treated patients and 0.87% TZD-treated patients, respectively (p=0.0002). The hazard ratio (HR) of AF was 0.846 (95% confidence interval [CI]: 0.0.775–0.923) in SGLT-2i-treated patients compared with TZD-treated patients. Conclusions In this study, the risk of AF development was significantly lower in patients treated with SGLT-2i versus TZD. SGLT2 would be a good choice for the patients with high risk of AF development among diabetes mellitus. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Incidence of atrial fibrillation in patients with diabetes mellitus: effect of sex, age and type of diabetes in a nationwide analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
L Fauchier ◽  
A Bisson ◽  
G Fauchier ◽  
A Bodin ◽  
J Herbert ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Incidence Rates ◽  
Diabetic Patients ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: None. Background. There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. Methods. All patients aged > =18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). Results. In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. During 13.5 million person-years of follow-up, 327,012 patients with new-onset AF were identified. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27-1.37) in women vs. 1.12(1.08-1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16-1.19) in women vs. 1.10(1.09-1.12) in men for type 2 diabetes.  The adjusted HRs for women were significantly higher than the adjusted HRs for men as shown with the adjusted women-to-men ratios (adjusted WMR = adjusted HR women compared to adjusted HR men) = 1.18 (95%CI 1.12-1.24) for type 1 diabetes and 1.10 (95%CI 1.08-1.12) for type 2 diabetes. This phenomenon was seen across all ages in men and women with type 1 diabetes and progressively decreased with advancing age.  In type 2 diabetes, this phenomenon was seen after 50 years, increased until 60-65 years and then progressively decreased with advancing age. Conclusion. Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.

3269Impact of type 2 diabetes on incidence and phenotype of heart failure in patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Polovina ◽  
I Milinkovic ◽  
G Krljanac ◽  
I Veljic ◽  
I Petrovic-Djordjevic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
History Of ◽  
New Onset

Abstract Background Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised. Purpose In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up. Methods We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF. Results Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%). Conclusions T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.

scholarly journals Sex, age, type of diabetes and incidence of atrial fibrillation in patients with diabetes mellitus: a nationwide analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Arnaud Bisson ◽  
Alexandre Bodin ◽  
Grégoire Fauchier ◽  
Julien Herbert ◽  
Denis Angoulvant ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Incidence Rates ◽  
Diabetic Patients ◽  
Diabetes Status ◽  
History Of

Abstract Background There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. Methods All patients aged ≥ 18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). Results In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27–1.37) in women vs. 1.12(1.08–1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16–1.19) in women vs. 1.10(1.09–1.12) in men for type 2 diabetes. Conclusion Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.

P0751METFORMIN, A CLASSIC TREATMENT FOR TYPE 2 DIABETES WITH POSSIBLE RENOPROTECTIVE EFFECTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Adriana Acosta Barrios ◽  
Marian Goicoechea ◽  
Eduardo Verde ◽  
Ángela González-Rojas ◽  
Andres Delgado ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Experimental Studies ◽  
Diabetic Patients ◽  
Metformin Treatment ◽  
End Point ◽  
Progression Of Kidney Disease

Abstract Background and Aims Metformin is the antidiabetic of choice in patients with type 2 diabetes mellitus. Experimental studies and clinical observations have shown that metformin could have a beneficial effect on the progression of kidney disease through the activation of cAMP due to its anti-inflammatory, antifibrotic, and anti-oxidative action. The objective was to compare the progression of CKD in diabetic patients with or without metformin as antidiabetic in their treatment and the prevalence of cardiovascular events in both groups. Method Unicentric retrospective observational analysis. Inclusion criteria: outpatients seen in nephrology consultation during the year of 2012 with diabetes mellitus and stage 3 CKD. Renal, cardiovascular outcomes and mortality were analyzed between patients treated with / without metformin. Median follow-up of 76.5 months (41-84). Renal end-point: estimated glomerular filtration rate drop (MDRD-4) by 50% and / or start of dialysis program. Cardiovascular end-point: ischemic heart disease, stroke, arterial revascularization and / or amputation. Cardiovascular or any cause mortality. Results 148 patients (96M, 52W) with a mean age of 75±9 years and an eGFR of 40±9 ml / min / 1.73 m2 were included. In relation to hypoglycemic therapy: 45 received metformin, 61 insulin and 31 DPP4i. 80% received treatment with RAAS blockers. After the follow-up, the progression of the renal disease was greater in patients who did not receive metformin: eGFR fall of -7.0±16 vs -0.15±16 ml / min in those treated with metformin (p = 0.019). 25 patients in the group without metformin suffered a renal event vs. 5 in the metformin group (logRank: 4.186, p = 0.045). In the Cox analysis, metformin treatment decreases the progression of kidney disease in a model adjusted for baseline renal function and treatment with RAASB (HR 0.368, p = 0.043), losing its predictive power in a proteinuria-adjusted model. During the follow-up, 45 patients died (20 metformin, 25 non-metformin) and 45 patients suffered a cardiovascular event (15 metformin, 30 non-metformin), with no differences between the two groups. Conclusion Metformin treatment in patients with stage 3 CKD could slow the progression of CKD, this effect should be demonstrated in randomized studies with larger sample size.

scholarly journals Awaking Blood Pressure Surge and Progression to Microalbuminuria in Type 2 Normotensive Diabetic Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michelangela Barbieri ◽  
Maria Rosaria Rizzo ◽  
Ilaria Fava ◽  
Celestino Sardu ◽  
Nicola Angelico ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cox Regression ◽  
Blood Pressure Monitoring ◽  
Adult Patients ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Pressure Surge

Background. We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes.Methods. Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP.Results. After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (−0.67±1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86±6.92 mmHg) during follow-up were 17.41 (95% CI 6.26–48.42);pfor trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6[1.4]to 36.8[7.1],p<0.001.Conclusion. An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.

scholarly journals Sodium-glucose co-transporter-2 inhibitors and the risk of major arrhythmias: a meta-analysis of the cardiovascular and renal outcome trials

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Boulmpou ◽  
D Patoulias ◽  
E Teperikidis ◽  
C E Papadopoulos ◽  
P Sarafidis ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Atrial Flutter ◽  
Atrioventricular Block ◽  
Meta Analysis ◽  
Renal Outcome ◽  
Diabetic Patients

Abstract Background Type 2 diabetes mellitus is closely associated with cardiovascular disease and evidence already exists on its arrhythmogenic action. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a unique class of oral antidiabetic medications which recently attracted attention for reducing the total risk of major adverse cardiovascular events in a series of recent, large placebo-controlled randomized clinical trials (RCTs). Dapagliflozin and empagliflozin additionally seem to improve survival and outcomes in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of diabetes mellitus. Whether antidiabetic treatment with sodium-glucose co-transporter inhibitors could reduce the arrhythmic burden in diabetic patients still is to be clarified. Purpose The purpose of the present meta-analysis was to report the impact of SGLT2i on the risk for several types of cardiac arrhythmias, pooling data from all relevant cardiovascular and renal outcome, placebo-controlled, RCTs, comparing SGLT2i to placebo. Methods We searched PubMed for all available cardiovascular and renal outcome RCTs utilizing SGLT2i, along with grey literature sources. We sought to determine the risk of the following arrhythmias/cardiac disorders with the use of SGLT2i versus placebo: atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, ventricular extrasystoles, sinus bradycardia, sinus node dysfunction, second degree atrioventricular block, complete atrioventricular block. Results We extracted relevant data from 8 trials (5 dedicated cardiovascular outcome trials, 2 dedicated renal outcome trials, 1 trial enrolling patients with HFrEF), pooling data in a total of 55,966 patients. SGLT-2i treatment compared to placebo produced a significant reduction in the risk of atrial fibrillation equal to 21% (RR=0.79, 95% CI: 0.67–0.93, I2=0%) (Figure 1). A non-significant reduction in the risk of atrial flutter equal to 9% (RR=0.91, 95% CI: 0.64–1.29, I2=0%) was also observed with SGLT2i (Figure 2). No significant effect on the rest major arrhythmias was observed. Conclusions Antidiabetic therapy with SGLT2i seems to hold a significant impact on antiarrhythmic burden in type 2 diabetes mellitus, reducing the risk of atrial fibrillation development. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Follow-up and treatment pattern during Ramadan and evaluation of the outcome of Ramadan fasting on clinical, biochemical and metabolic parameters in patients with type 2 diabetes mellitus: a realworld, multi-center, prospective observational study

2020 ◽  
Vol 11 (1) ◽  
pp. 30-38
Author(s):  
Nazmul Kabir Qureshi ◽  
Nazma Akter ◽  
Zafar Ahmed
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Prospective Observational Study ◽  
Treatment Pattern ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Ramadan Fasting ◽  
Type 2 Diabetic

Background: There are variable effects of Ramadan fasting on clinical and biochemical variables of diabetic people. Anti-diabetic agents are often adjusted during this time to reflect changes in lifestyle. The study was conducted to understand the diversity of follow-up, treatment pattern, clinical, and biochemical outcome of Ramadan fasting among type 2 diabetic patients who observed Ramadan fast. Methods: This real-world, multi-center, prospective, observational study was conducted at the diabetes outpatient department of National Healthcare Network (NHN) Uttara Center of Bangladesh Diabetic Somity (BADAS), Dhaka, Bangladesh and outpatient department of MARKS Hormone and Diabetes clinic, MARKS Medical College &Hospital in Dhaka, Bangladesh upon randomly selected type 2 diabetic patients, recruited 1 to 12 weeks prior to the Ramadan and followed up till 12 weeks post-Ramadan period. Finally, a total of 271 participants completed satisfactory follow up. Data was collected before, during, and after Ramadan using a set of questionnaires in a face to face interview. Results: The majority (80.1%) of participants received pre-Ramadan education, counseling, adjustment of medication and other direction to help them cope with Ramadan fasting. A significant reduction of weight, body mass index (BMI)) and blood pressure were reported after Ramadan fast (p<0.001). None of the studied participants experienced severe hyper/hypoglycemia or acute complications requiring hospitalization or an emergency room visit. Metformin was the commonest prescribed anti-diabetic medication. Premixed insulin was the commonest insulin regimen during study period. Three most commonly adjusted oral anti-diabetic drugs were gliclazide, glimepiride, metformin and insulin doses were also adjusted. Mean of fasting and prandial capillary blood glucose decreased from pre-Ramadan period to post-Ramadan period (P<0.05). HbA1c decreased during post-Ramadan period compared to pre-Ramadan visit (P=0.13). A significant reduction in the triglyceride level was observed during post-Ramadan follow up (P< 0.05). Conclusion: The study revealed that a safe fasting can be observed with proper pre-Ramadan work-up. Ramadan fasting resulted into significant reduction of weight, BMI, blood pressure, lipid profile and improved glycemic status in patients with type 2 diabetes. Birdem Med J 2021; 11(1): 30-38

scholarly journals Aortic plaques in patients with atrial fibrillation: an often-forgotten risk factor for thromboembolism

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.F Esteves ◽  
L Parreira ◽  
M Fonseca ◽  
J.M Farinha ◽  
J Ferreira ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
P Value ◽  
Af Ablation ◽  
Aortic Plaques ◽  
Af Recurrence

Abstract Background CHA2DS2-VASc risk score is the main determinant for maintaining anticoagulation after atrial fibrillation (AF) ablation, irrespective of the procedure outcome. The presence of aortic plaques is included in the score, but isn't regularly assessed previously to AF ablation. This way, risk factors for coronary artery disease (CAD) other than arterial hypertension and diabetes mellitus may influence stroke risk in patients with AF, albeit not being included in the CHA2DS2-VASc score. Purpose We sought to evaluate the prevalence of aortic plaques diagnosed during transesophageal echocardiography (TOE) in patients submitted to AF ablation and to assess its determinants and clinical impact on the CHA2DS2-VASc score. Methods Retrospective study of patients submitted to AF ablation that performed TOE prior to the procedure, with assessment of aortic plaques. CHA2DS2-VASc risk score was evaluated in the pre-ablation patient evaluation and reassessed after TOE. Demographic, clinical and echocardiographic data, including cardiovascular risk factors, were analyzed. We assessed AF recurrence rate, cerebrovascular events and death during follow-up. Results 120 patients were submitted to TOE prior to AF ablation from November 2015 to December 2020, mean age 66.6 (±9.55) years, 48% male. In 30 (25%) patients aortic plaques were identified in TOE. Mean CHA2DS2-VASc was 2.2 (±1.47) in pre-ablation evaluation and 2.5 (±1.69) post-TOE, increasing in all patients with aortic plaques and prompting beginning of oral anticoagulation in 5 patients. AF was paroxysmal in 74% and persistent in 26% of patients, mean duration of 6.28 (±3.76) years. Arterial hypertension was present in 79 (66%) of patients, type 2 diabetes mellitus in 24 (20%) and dyslipidemia in 67 (56%). 17 (14%) patients had a prior stroke. During a mean follow-up of 30 (±18.3) months, 32 (27%) patients had AF recurrence and 10 (8%) were submitted to redo procedures. 107 (89%) patients remained under oral anticoagulation, stroke occurred in 1 patient and 2 patients died. In univariate analysis, age, type 2 diabetes mellitus and dyslipidemia predicted an increase in CHA2DS2-VASc score after TOE (respectively, OR 1.113, 95% CI 1.041–1.190, p-value 0.002; OR 2.907, 95% CI 1.145–7.379, p-value 0.025; and OR 2.442, 95% CI 1.016–5.868, p-value 0.046). In multivariate analysis, age is the only independent predictor of increased CHA2DS2-VASc score after TOE (OR 1.095, 95% CI 1.013–1.185, p-value 0.023). No risk factor for CAD was independently associated with the presence of aortic plaques (Table 1). Conclusion In this population, single CAD risk factors were not independent predictors of aortic plaques. If TOE had not been performed prior to AF ablation, 25% of patients would have had an underestimated CHA2DS2-VASc score and would be off anticoagulation after the procedure, unprotected from thromboembolic events. FUNDunding Acknowledgement Type of funding sources: None. Table 1

scholarly journals Carbohydrate Quantity and Quality and Risk of Type 2 Diabetes: Results from Three Large Prospective US Cohorts

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1380-1380
Author(s):  
Kim Braun ◽  
Marta Liu Guasch-Ferré ◽  
Vasanti Malik ◽  
Hala Alessa ◽  
Walter Willett ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Saturated Fat ◽  
Whole Grains ◽  
Health Study ◽  
Monounsaturated Fat ◽  
Funding Sources ◽  
Cox Proportional Hazard Regression ◽  
Time Varying Covariates

Abstract Objectives Carbohydrate intake has been reported to be associated with higher type 2 diabetes (T2D) risk, but high and low quality of carbohydrate may have different effects. Furthermore, these effects may differ depending on overall macronutrient composition. We aimed to examine associations of isocalorically substituting high quality carbohydrates (HQC) and low quality carbohydrates (LQC) with other macronutrients on T2D risk. Methods We included 69,949 women from the Nurses’ Health Study, 90,239 women from the Nurses’ Health Study 2, and 40,539 men from the Health Professionals Follow-up Study. Dietary data were collected every 2–4 years using a semi-quantitative food frequency questionnaire, from which dietary intake of LQC and HQC were calculated. LQC was defined as the percentage of energy (E%) from carbohydrates from refined grains, sugary foods, and potatoes, and HQC as E% from carbohydrate from whole grains. Hazard ratios were estimated using Cox proportional hazard regression analyses with time-varying covariates. Results During 4389,996 years of follow-up, we documented 11,872 T2D cases. In pooled multivariable-adjusted analyses, substituting 5E% from saturated fat with 5E% from LQC was associated with a higher T2D (HR[95% CI] = 1.05[1.00–1.09]) while substitution with HQC was associated with a lower T2D risk (HR[95% CI] = 0.93[0.87–0.99]). Isocaloric substitution of other macronutrients with LQC was not associated with T2D risk. On the other hand, isocaloric substitution of HQC was associated with lower T2D risk when the replacement nutrient was monounsaturated fat (HR[95% CI] = 0.88[0.83–0.94]), polyunsaturated fat (HR[95% CI] = 0.92[0.86–0.98]), trans fat (HR[95% CI] = 0.90[0.85–0.97]), animal protein (HR[95% CI] = 0.88[0.83–0.93]), and vegetable protein (HR[95% CI] = 0.90[0.84–0.96]). Conclusions Our study suggests that higher intake of HQC, especially from whole grains, is associated with a lower T2D risk, irrespective of the macronutrient it replaces. In contrast, a higher intake of LQC is associated with a higher risk of type 2 diabetes, but only when it replaces saturated fat. Our findings highlight the importance of making a distinction between carbohydrate from high and low quality sources and taking into account different substitutions when examining macronutrients. Funding Sources National Institutes of Health.

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