Background Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. Methods A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. Results In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. Conclusions Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

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).

Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus

OBJECTIVE The Diabetes Control and Complications Trial (DCCT) was designed to test the glucose hypothesis and determine whether the complications of type 1 diabetes (T1DM) could be prevented or delayed. The Epidemiology of Diabetes Interventions and Complications (EDIC) observational follow-up determined the durability of the DCCT effects on the more-advanced stages of diabetes complications including cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS The DCCT (1982-1993) was a controlled clinical trial in 1,441 subjects with T1DM comparing intensive therapy (INT), aimed at achieving levels of glycemia as close to the nondiabetic range as safely possible, with conventional therapy (CON), which aimed to maintain safe asymptomatic glucose control. INT utilized three or more daily insulin injections or insulin pump therapy guided by self-monitored glucose. EDIC (1994-present) is an observational study of the DCCT cohort. RESULTS The DCCT followed >99% of the cohort for a mean of 6.5 years and demonstrated a 35-76% reduction in the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%. The major adverse effect of INT was a threefold increased risk of hypoglycemia, which was not associated with a decline in cognitive function or quality of life. EDIC showed a durable effect of initial assigned therapies despite a loss of the glycemic separation (metabolic memory) and demonstrated that the reduction in early-stage complications during the DCCT translated into substantial reductions in severe complications and CVD. CONCLUSIONS DCCT/EDIC has demonstrated the effectiveness of INT in reducing the long-term complications of T1DM and improving the prospects for a healthy life span.

https://care.diabetesjournals.org/content/diacare/37/1/9.full.pdf

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Overview

Diabetes mellitus is a disease of metabolic dysregulation, most notably abnormal glucose metabolism, accompanied by characteristic long-term complications. The complications that are specific to diabetes include retinopathy, nephropathy, and neuropathy. Patients with all forms of diabetes of sufficient duration, including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), are vulnerable to these complications, which cause serious morbidity (Table 1 and Table 2). Retinopathy is so characteristic of diabetes that its presence has been incorporated into the nosologic definition of NIDDM. Only hyperglycemia of sufficient magnitude to be associated with retinopathy is classified as NIDDM, while lower levels of hyperglycemia that are . . .

Long-term complications of diabetes mellitus

In 307 patients with diabetes mellitus, developed prior to 1933 and before age 31 it was demonstrated that: (1) frequent contact with a specialized diabetes clinic from an early stage of the disease; (2) a good quality of “metabolic control”; (3) a low insulin dose; (4) a body weight of 10% less than ideal; and (5) a mean blood pressure below 100 mm Hg, all had significantly beneficial effects upon the survival. It was also found that patients domiciled in Copenhagen had a significantly better prognosis than patients domiciled outside Copenhagen. Frequent contact with a diabetes centre was accompanied by an appreciable decrease in disabling late diabetic complications.

https://link.springer.com/content/pdf/10.1007/BF01228131.pdf

Prognosis of diabetics with diabetes onset before the age of thirty-one. I. Survival, causes of death, and complications

In 307 patients with diabetes mellitus, developed prior to 1933 and before age 31 it was demonstrated that: (1) frequent contact with a specialized diabetes clinic from an early stage of the disease; (2) a good quality of "metabolic control"; (3) a low insulin dose; (4) a body weight of 10% less than ideal; and (5) a mean blood pressure below 100 mm Hg, all had significantly beneficial effects upon the survival. It was also found that patients domiciled in Copenhagen had a significantly better prognosis than patients domiciled outside Copenhagen. Frequent contact with a diabetes centre was accompanied by an appreciable decrease in disabling late diabetic complications.

/pdf/prognosis-of-diabetics-with-diabetes-onset-before-the-age-of-42h4kk67tv.pdf

Prognosis of diabetics with diabetes onset before the age of thirty-one. II. Factors influencing the prognosis.

The aim of this study was to determine whether metabolic control, treatment of complications, education and social support have really been of benefit to our juvenile diabetic population.

The prognosis of insulin dependent diabetes mellitus and the importance of supervision.

The object of this study was to investigate whether outpatient follow-up visits to a subspecialized clinic have a favorable effect upon length of life of juvenile diabetic patients, and to evaluate whether the cost of suchoutpatient supervision is in reasonable proportion to the benefit obtained. The study comprises 180 insulin-dependent diabetic patients in whom a diagnosis had been made before 1933, and before they were 31 years of age. The patients had been admitted to the Steno Memorial Hospital before their fifteenth year of diabetes. Sixteen patients could not be traced after forty years of diabetes, while the others were followed until death or until their fortieth year with diabetes. Seventy-seven patients never attended follow-up in the outpatient clinic, while the others attended one to 145 times in thecourse of their first twenty years of diabetes. From the results it is apparent that the duration of diabetes correlated with increased frequency of outpatient follow-up. With 4.4 annual outpatient follow-up visits, the duration of diabetes was prolonged by 11.9 years. The cost of this was estimated at $10,468 per patient over forty years. The benefit per patient over the entire forty years was $100,656. These findings suggest that outpatient supervision of diabetes in a subspecialized clinic is beneficial for patients and involves relatively little cost.

Larsen M

Papers

Prognosis of diabetics with diabetes onset before the age of thirty-one. I. Survival, causes of death, and complications

Prognosis of diabetics with diabetes onset before the age of thirty-one. II. Factors influencing the prognosis.

The prognosis of insulin dependent diabetes mellitus and the importance of supervision.

Importance of Outpatient Supervision in the Prognosis of Juvenile Diabetes Mellitus: A Cost/Benefit Analysis

Prognosis in juvenile diabetes mellitus. II. Factors of significance for the prognosis