This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.

/pdf/2019-esc-guidelines-on-diabetes-pre-diabetes-and-4treq2fwvr.pdf

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†.

In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC.

The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

 
| Classes of recommendations |
|:-------------------------- | ------------------------------------------------------------------------------------------------------------------------ |
| Class I | Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure |
|  Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy |
|  Class IIb | Usefulness/efficacy is less well established by evidence/opinion |
| Class III | Evidence or general agreement that the treatment or procedure is not useful/effective and, in some cases, may be harmful |

Diabetes and cardiovascular diseases (CVD) often appear …

/pdf/guidelines-on-diabetes-pre-diabetes-and-cardiovascular-4j63bs7fb2.pdf

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

/pdf/esc-guidelines-on-diabetes-pre-diabetes-and-cardiovascular-7k2pvnsifc.pdf

ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD)

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(97)03062-6.pdf

UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P 5 relative units) in patients older than 35 years at onset of type 2 diabetes.

Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies.

OBJECTIVE— To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients.

RESEARCH DESIGN AND METHODS— β-cell function in type II diabetic patients with ( n = 11, 50 ± 5 yr of age) and without ( n = 10, 52 ± 4 yr of age) ICA was followed prospectively and compared with β-cell function in type I adult diabetic patients ( n = 17, 37 ± 5 yr of age) and in healthy control subjects ( n = 34, age 45 ± 3 yr). β-cell function was evaluated as fasting C-peptide, 1 + 3 min C-peptide after intravenous glucose, and ∆ C-peptide after glucagon.

RESULTS— Fasting C-peptide was equal in type II diabetic patients with ICA (0.30 ± 0.03 nM) and type I diabetic patients (0.24 ± 0.03 nM) at diagnosis, and decreased ( P < 0.05) during 3 yr in these groups but not in type II diabetic patients without ICA. At diagnosis, type II diabetic patients with ICA showed a 1 + 3 min C-peptide (0.92 ± 0.17 nM) lower ( P < 0.001) than control subjects but higher ( P < 0.05) than type I diabetic patients (0.53 ± 0.11 nM). After 1 yr, 1 + 3 min C-peptide in type II diabetic patients with ICA had decreased ( P < 0.05) to 0.18 ± 0.11 nM and was equal to type I diabetic patients (0.38 ± 0.10 nM). ∆ C-peptide after glucagon was equally impaired in type II diabetic patients with ICA (0.38 ± 0.06 nM) and type I diabetic patients (0.35 ± 0.11 nM) at diagnosis. After 3 yr, type II diabetic patients with ICA had fasting C-peptide of 0.09 ± 0.04 nM, 1 + 3 min C-peptide of 0.18 ± 0.10 nM, and ∆ C-peptide after glucagon of 0.20 ± 0.09 nM, values equal to type I diabetic patients but lower ( P < 0.01) than in type II diabetic patients without ICA, whose values remained unchanged; fasting C-peptide of 0.97 ± 0.17 nM, 1 + 3 min C-peptide of 2.31 ± 0.50 nM, and ∆ C-peptide after glucagon of 1.76 ± 0.28 nM.

CONCLUSIONS— In patients considered type II diabetic with ICA, β-cell function progressively decreased after diagnosis, and after 3 yr was similar to type I diabetic patients, whereas β-cell function in type II diabetic patients without ICA was unchanged.

β-Cell Function in Relation to Islet Cell Antibodies During the First 3 Yr After Clinical Diagnosis of Diabetes in Type II Diabetic Patients

Glutamate decarboxylase antibody levels predict rate of β-cell decline in adult-onset diabetes

Aims: To clarify whether parasympathetic neuropathy in Type 2 diabetic patients is associated with features of the insulin resistance syndrome. Methods: Blood pressures, glycaemic control (HbA(IC)), plasma lipids, residual β-cell function (fasting plasma C-peptide), autonomic nerve function, urinary albumin excretion and glomerular filtration rate (Cr-EDTA clearance) were evaluated in 82 Type 2 diabetic patients (age 61 ± 1 years) 5 years after diagnosis of diabetes. Results: Parasympathetic neuropathy (an abnormal age corrected E/I ratio) was found in 24/82 (29%) patients. After adjustment for body mass index (BMI), patients with parasympathetic neuropathy had elevated fasting plasma C-peptide (P < 0.001) and triglyceride (Tg) (P < 0.05) levels compared with patients without parasympathetic neuropathy. In addition, the age corrected E/I ratio correlated inversely with Tg (r = -0.31; P < 0.01) and fasting plasma C-peptide (r = -0.32; P < 0.01) in the Type 2 diabetic patients. Conclusion: Autonomic neuropathy 5 years after diagnosis of Type 2 diabetes is associated with an unfavourable metabolic risk profile. (Less)

Autonomic neuropathy in Type 2 diabetic patients is associated with hyperinsulinaemia and hypertriglyceridaemia

To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43±3 years), 55 nonobese ICA-negative (mean age at diagnosis 58±2 years), 7 obese ICA-positive (mean age at diagnosis 57±5 years), and 139 obese ICA-negative (mean age at diagnosis 58±1 years). Fasting C-peptide decreased (P<0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6±0.6 versus 24.5±0.4;P<0.05), lower fasting C-peptide (0.14±0.06 nmol/l versus 0.71±0.07 nmol/l;P<0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%);P<0.001] than nonobese ICA-negative patients. In obese ICA-positive patients, fasting C-peptide also decreased (Δ C-peptide 0.17±0.04 nmol/l;P<0.05) after diagnosis, and 3 years after diagnosis, obese ICA-positive patients showed lower BMI (25.7±1.2 versus 29.8±0.4;P<0.01) and fasting C-peptide (0.08±0.04 nmol/l versus 1.06±0.05 nmol/l;P<0.001) and higher HbA1c values (9.92%±0.68% versus 7.39%±0.21%;P<0.01) and a higher frequency of insulin treatment [7/7 (100%) versus 5/121 (4%);P<0.001] than obese ICA-negative patients. Therefore, ICA detected at diagnosis of diabetes in both obese and nonobese adult patients indicate β-cell dysfunction, high HbA1c levels, and progression to insulin dependency.

Islet cell antibodies are associated with β-cell failure also in obese adult onset diabetic patients

Insulin and C-peptide responses to 0.5 g kg−1 intravenous glucose and 1.0 mg glucagon were studied in 34 healthy subjects (age 19-78 years, mean 45). Fasting blood glucose (r=0.59; p<0.001) and glycosylated haemoglobin (r=0.61; p<0.001) increased with age, but not the initial C-peptide and insulin responses to the glucose infusion. However, the C-peptide response at 70 min (r=0.36; p<0.05), 80 min (r=0.41; p<0.05), and 90 min (r=0.46; p<0.01) after the glucose infusion correlated with age as well as both insulin (r=0.42; p<0.05) and C-peptide (r=0.45; p<0.05) responses to the glucagon injection. Reproducibility of insulin and C-peptide responses was evaluated by duplicate tests, separated 2-143 days in time, in 10 healthy subjects (age 19-48 years, mean 32 years) showing no significant differences in median within-subject variation between the initial (1+3 min) or overall (0-90 min area under curve) insulin (24% and 17%, respectively) and C-peptide (15% and 14%, respectively) responses to glucose, while t...

Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and C-peptide to measure insulin secretion

P. Fernlund

Papers

β-Cell Function in Relation to Islet Cell Antibodies During the First 3 Yr After Clinical Diagnosis of Diabetes in Type II Diabetic Patients

Glutamate decarboxylase antibody levels predict rate of β-cell decline in adult-onset diabetes

Autonomic neuropathy in Type 2 diabetic patients is associated with hyperinsulinaemia and hypertriglyceridaemia

Islet cell antibodies are associated with β-cell failure also in obese adult onset diabetic patients

Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and C-peptide to measure insulin secretion