Browsing by Author "Lalić, Nebojša M. (13702597500)"

This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05) and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001). HOMA-IR was higher in group A versus group B (P<0.05) and in C versus D (P<0.01). Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05) and in C versus D (P<0.01), while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis. © 2015 Katarina Lalić et al.

This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05) and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001). HOMA-IR was higher in group A versus group B (P<0.05) and in C versus D (P<0.01). Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05) and in C versus D (P<0.01), while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis. © 2015 Katarina Lalić et al.

Introduction Several cardiovascular manifestations in patients with diabetes may be asymptomatic. Left ventricular diastolic dysfunction (LVDD) is considered to be the earliest metabolic myocardial lesion in these patients, and can be diagnosed with tissue Doppler echocardiography. Silent myocardial ischemia (SMI) is a characteristic and frequently described form of ischemic heart disease in patients with diabetes. Objective The aim of the study was to assess the prevalence of LVDD and SMI in patients with type 2 diabetes, as well as to compare demographic, clinical, and metabolic data among defined groups (patients with LVDD, patients with SMI and patients with type 2 diabetes, without LVDD and SMI). Methods We investigated 104 type 2 diabetic patients (mean age 55.4±9.1 years, 64.4% males) with normal blood pressure, prehypertension and arterial hypertension stage I. Study design included basic laboratory assessment and cardiological workup (transthoracic echocardiography and tissue Doppler as well as the exercise stress echocardiography). Results LVDD was diagnosed in twelve patients (11.5%), while SMI was revealed in six patients (5.8%). Less patients with LVDD were using metformin, in comparison to other two groups (χ2 =12.152; p=0.002). Values of HDL cholesterol (F=4.515; p=0.013) and apolipoprotein A1 (F=5.128; p= 0.008) were significantly higher in patients with LVDD. Conclusion The study confirmed asymptomatic cardiovascular complications in 17.3% patients with type 2 diabetes.

Aims/hypothesis: Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Methods: Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Results: Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). Conclusions/interpretation: We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Aims: This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED). Methods: ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED− N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis. Results: Si was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min−1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED− group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED− groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size. Conclusions: Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes. © 2018 Elsevier B.V.

Aims: This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED). Methods: ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED− N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis. Results: Si was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min−1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED− group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED− groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size. Conclusions: Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes. © 2018 Elsevier B.V.

Aims: This systematic review was aimed to assess the association between magnitude of body weight loss (BWL) in type 2 diabetes (T2D) patients and cardiovascular (CV) risk in CV outcome trials (CVOTs). Methods: We searched electronic databases (PubMed, Cochrane and Scopus) for available CVOTs, observational cohort studies or post hoc analyses of clinical trials of adult T2D patients investigated the association of BWL with CV outcomes and/or all-cause mortality. Results: 19 RCTs of novel glucose-lowering drugs (GLP-1RA, DPP-4i and SGLT2i) and 6 RCT or observational trial of different strategies (intensive treatment or standard care) were included (379.904 T2D patients). Higher BWL during GLP-1RA treatment, in comaprison to lower BWL, was associated with higher decrease in risk of MACE, while DPP-4i had not that effect. With SGLT2i the higher decrease in risk of MACE was associated with lower BWL. In contrast, in other different strategies, higher BWL lead to increase in risk for MACE and all-cause mortality. Conclusions: In CVOTs, treatment of T2D patients resulted in BWL, which correlated with reduction in risk for CV outcomes, particularly with GLP-1 RAs. However, interventional non-CVOTs are warning that in the absence of structured behavioral intervention and relevant medication, the large BWL might be harmful for CV outcomes. © 2024 Elsevier B.V.

Aims: This systematic review was aimed to assess the association between magnitude of body weight loss (BWL) in type 2 diabetes (T2D) patients and cardiovascular (CV) risk in CV outcome trials (CVOTs). Methods: We searched electronic databases (PubMed, Cochrane and Scopus) for available CVOTs, observational cohort studies or post hoc analyses of clinical trials of adult T2D patients investigated the association of BWL with CV outcomes and/or all-cause mortality. Results: 19 RCTs of novel glucose-lowering drugs (GLP-1RA, DPP-4i and SGLT2i) and 6 RCT or observational trial of different strategies (intensive treatment or standard care) were included (379.904 T2D patients). Higher BWL during GLP-1RA treatment, in comaprison to lower BWL, was associated with higher decrease in risk of MACE, while DPP-4i had not that effect. With SGLT2i the higher decrease in risk of MACE was associated with lower BWL. In contrast, in other different strategies, higher BWL lead to increase in risk for MACE and all-cause mortality. Conclusions: In CVOTs, treatment of T2D patients resulted in BWL, which correlated with reduction in risk for CV outcomes, particularly with GLP-1 RAs. However, interventional non-CVOTs are warning that in the absence of structured behavioral intervention and relevant medication, the large BWL might be harmful for CV outcomes. © 2024 Elsevier B.V.

Background: Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease. Methods: The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia (≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated. Results: Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same. Conclusion: Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control. © 2019 The Author(s).

The cardiovascular complications of type 2 diabetes (T2DM) are contributing considerably to morbidity and mortality worldwide, heart failure (HF) being one of the most frequent. The adverse effect of T2DM on myocardium can develop early, and clinically present as left ventricular (LV) diastolic dysfunction in the absence of other heart disease. The pathophysiology of DC includes the major metabolic features of T2DM such as hyperglycemia, hyperinsulinemia, hyperlipidemia, and the formation of both reactive oxygen species and advanced glycation end-products. There are no pathognomonic diagnostic features of diabetic cardiomyopathy (DC) and no single imaging method exists for the accurate diagnosis. Clinical presentation is mostly mild, and majority of the patients are asymptomatic or with nonspecific complaints. The major hurdles in diagnosing DC are imprecise definition and dissimilar criteria for diagnosis of LV diastolic dysfunction. DC is best defined as myocardial disease in diabetic patients characterized by LV diastolic dysfunction in the absence of hypertension, coronary artery disease or any other cardiac disease. LV diastolic dysfunction is the most important element of diagnosis of DC, best assessed by tissue Doppler echocardiography (E/E' ratio). The prevalence of LV diastolic dysfunction in T2DM demonstrate the wide variations caused by diverse patient selection and heterogeneous criteria for its diagnosis. Patient selection varies in terms of age, duration, stage, and microvascular complications of T2DM. Several clinical correlates were reported as related to DC such as: age, duration of T2DM, parameters of glycoregulation, insulin resistance, and renal function. The treatment of DC should be initiated as early as LV diastolic dysfunction is identified. Various therapeutic options include improving diabetic control with diet, daily physical activity, and reduction in body mass index. Both antiglycaemic (metformin and thiazolidinediones), and cardiovascular drugs (ACE inhibitors, beta blockers and calcium channel blockers) should be used to improve LV diastolic dysfunction. © 2014 by Nova Science Publishers, Inc. All rights reserved.

[No abstract available]

Background: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents.; Methods: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty.; Conclusion: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.; Results: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). © by Mirjana Kocova 2014.

Background: Prediabetes is characterized by isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT. This study aimed to establish the prevalence of prediabetes and examine possible contributory factors in a cohort of obese adolescents.; Methods: In this prospective study, we recruited 85 obese patients from the Obesity Clinic at the University Children's Hospital and 17 normal weight controls. All patients were of Caucasian origin, 60 males/42 females, aged 7.4-18.3 years, with at least Tanner 2 stage of puberty.; Conclusion: Prediabetes occurrence was fairly high in our obese adolescents. Further studies should establish what would be the most appropriate screening test to diagnose these patients at risk for type 2 diabetes and initiate treatment without delay.; Results: Depending on criteria we used, insulin resistance was confirmed in 62-100% of obese patients, predominantly in the group with BMI SDS > 3. oGTT revealed isolated impaired fasting glucose (IFG) in 13.9%, impaired glucose tolerance (IGT) in 20.8% and combined IFG and IGT only in 2.8% of the obese patients. Patients in the prediabetes group were older (14±2.4 vs 12.8±2.5 p=0.04) and had higher glucose levels (p<0.001) during the whole oGTT compared to normal glucose tolerance (NGT) group. There was no difference between groups in respect to family history, BMI, lipids and fasting insulin. Insulinogenic index, WBISI and HOMA%B were significantly lower in the prediabetes group compared to the NGT group (p=0.07, 0.01 and 0.04 respectively). HbA1c level was measured in 58% of patients and was significantly higher in the prediabetes group (5.4±0.3 vs 5.7±0.4, p=0.002). © by Mirjana Kocova 2014.

Background and aims: Despite the use of statins, familial hypercholesterolemia (FH) patients often have increased LDL-cholesterol (Ch) and high risk for atherosclerotic cardiovascular disease (ASCVD). This study aimed to analyze the effect of statin therapy on attainment of LDL-Ch treatment targets and appearance of new ASCVD and diabetes in FH patients. Methods: This study is a retrospective analysis of data from medical records of 302 FH patients treated continuously with statins during 3 years. At baseline and once yearly, anthropometric measurements, lipids (total Ch, LDL-Ch, HDL-Ch, triglycerides, apoliporotein A1 and B), fasting plasma glucose, and insulin were determined. Results: In FH patients, high intensity statin was prescribed only in 17.9% of cases. LDL-Ch levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; p < 0.01), but only 6.9% of FH patients reached the recommended ≥50% LDL-Ch reduction and 16.2% attained the LDL-Ch <2.6 mmol/l target. Simultaneously, 9.6% of FH patients developed new ASCVD, with lower HDL-Ch after 3 years of statin treatment than in those who remained free of ASCVD. In addition, we observed new onset diabetes in 6.4% of FH patients who were more obese, older and with higher fasting glucose at baseline than FH patients free of diabetes, regardless of the type of statin. Conclusions: These results imply that only a small proportion of FH patients achieved the recommended LDL-Ch treatment targets, mostly due to the use of low statin dose and infrequent implementation of high-intensity statin treatment, which altogether could not prevent the increase in residual cardiovascular risk. © 2018 Elsevier B.V.

Background: We assessed the effect of structured self-monitoring of blood glucose (SMBG), in combination with intensive education, on metabolic control, SMBG frequency, hospitalizations, cardiovascular risk factors, and quality-of-life parameters in patients with insulin-treated diabetes in primary health care settings in Serbia. Methods: This 6-month, observational, noninterventional study, followed 346 insulin-treated diabetes patients (type 1 diabetes [T1D], n = 57; type 2 diabetes [T2D], n = 289) from 28 primary care centers. Patients attended a 10-day course at the specialized educational center and were followed monthly by their primary care physicians. Patients used a simple paper tool to document 3-day, 7-point glucose profiles prior to each monthly clinic visit. Physicians reviewed the completed forms at each visit and used a standardized education program to provide remedial training. Changes in HbA1c levels, SMBG frequency, metabolic risk factors, and Diabetes Distress Scale (DDS) were assessed. Results: Mean (± SD) HbA1c within the full cohort was significantly improved from baseline at 6 months (8.85 ± 1.17% vs 7.91 ± 1.24%, P <.01). Significant increases in average SMBG frequency per week were seen at 6 months versus baseline (14.6/week vs 4.3/week, P <.001). The mean (± SE) number of hospitalizations due to metabolic conditions was significantly lower during the 6-month study compared to the 6-month period prior to the study (0.14 ± 0.04 vs 0.59 ± 0.09). DDS scores decreased from 39.6 ± 13.9 to 33.9 ± 14.5, P <.01. Conclusion: The use of structured SMBG combined with intensive education was associated with clinically significant reductions in HbA1c, increased SMBG frequency, and improved quality of life. © Diabetes Technology Society.

Background: We assessed the effect of structured self-monitoring of blood glucose (SMBG), in combination with intensive education, on metabolic control, SMBG frequency, hospitalizations, cardiovascular risk factors, and quality-of-life parameters in patients with insulin-treated diabetes in primary health care settings in Serbia. Methods: This 6-month, observational, noninterventional study, followed 346 insulin-treated diabetes patients (type 1 diabetes [T1D], n = 57; type 2 diabetes [T2D], n = 289) from 28 primary care centers. Patients attended a 10-day course at the specialized educational center and were followed monthly by their primary care physicians. Patients used a simple paper tool to document 3-day, 7-point glucose profiles prior to each monthly clinic visit. Physicians reviewed the completed forms at each visit and used a standardized education program to provide remedial training. Changes in HbA1c levels, SMBG frequency, metabolic risk factors, and Diabetes Distress Scale (DDS) were assessed. Results: Mean (± SD) HbA1c within the full cohort was significantly improved from baseline at 6 months (8.85 ± 1.17% vs 7.91 ± 1.24%, P <.01). Significant increases in average SMBG frequency per week were seen at 6 months versus baseline (14.6/week vs 4.3/week, P <.001). The mean (± SE) number of hospitalizations due to metabolic conditions was significantly lower during the 6-month study compared to the 6-month period prior to the study (0.14 ± 0.04 vs 0.59 ± 0.09). DDS scores decreased from 39.6 ± 13.9 to 33.9 ± 14.5, P <.01. Conclusion: The use of structured SMBG combined with intensive education was associated with clinically significant reductions in HbA1c, increased SMBG frequency, and improved quality of life. © Diabetes Technology Society.

The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium–glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D. © 2020, The Author(s).