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.
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.
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.
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.
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.
•A small proportion of familial hypercholesterolemia (FH) patients achieved the recommended LDL-Ch treatment targets.•High intensity statin was prescribed in only 17.9% of FH patients.•9.6% of FH patients developed new atherosclerotic cardiovascular disease (ASCVD) during the 3 years of statin treatment.•New onset diabetes was diagnosed in 6.4% of statin treated FH patients.
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.
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.
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.
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.
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.
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.
In recent years, many studies have revealed the importance of heart failure (HF) development in type 2 diabetes (T2D), which increases the morbidity and mortality during the course of diabetes. In ...this context, it became important to emphasize the role of both cardiologists and diabetologists in the early diagnosis and further adequate treatment of HF in T2D. While HF appears in two major forms, with reduced or preserved ejection fraction (EF), namely HFrEF and HFpEF, it became important to define the optimal approach to the diagnostics. Regarding HFrEF, the role of cardiological methods remained dominant, while the complexity of early diagnosis requires nowadays more active participation of diabetologists. The absence of abundant symptoms and echocardiographic findings imposed the need for the use of risk markers based on metabolic variables and low-grade inflammation parameters. Following that unmet need, numerous studies have defined the possible relationship between metabolic variables in diabetes and the risk for HF. Moreover, attempts have been made to integrate biochemical and clinical parameters into risk score engines and some of them gave promising results. However, the follow-up studies in T2D subjects are needed to determine the clinical relevance of these new approaches.
Targeting Mitochondria in Diabetes Krako Jakovljevic, Nina; Pavlovic, Kasja; Jotic, Aleksandra ...
International journal of molecular sciences,
06/2021, Letnik:
22, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to ...disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.
•Coronary ED is associated with insulin resistance.•Coronary ED is also associated with impairments in insulin secretory response.•Decreases in LDL particle size, not the total LDL-Ch, influences ...coronary ED.•Coronary ED is also influenced by impaired fibrinolysis.
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).
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.
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.
Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.
This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed ...by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients.
This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo. The primary end point was change from baseline to week 26 in HbA
. The confirmatory secondary end point was change from baseline to week 26 in body weight.
In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA
8.0% 64 mmol/mol), oral semaglutide reduced HbA
(placebo-adjusted treatment differences at week 26: treatment policy estimand, -0.6% 3 mg, -0.9% 7 mg, and -1.1% 14 mg; trial product estimand, -0.7% 3 mg, -1.2% 7 mg, and -1.4% 14 mg;
< 0.001 for all) and body weight (treatment policy, -0.1 kg 3 mg, -0.9 kg 7 mg, and -2.3 kg 14 mg,
< 0.001; trial product, -0.2 kg 3 mg, -1.0 kg 7 mg,
= 0.01, and -2.6 kg 14 mg,
< 0.001). Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide. Trial product discontinuations occurred in 2.3-7.4% with oral semaglutide and 2.2% with placebo.
In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA
(all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists.
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