mellitus may be distinguished.
Prediabetes is characterized by the presence of islet cell autoantibodies in blood serum without metabolic disorders. Clinically important types are antibodies against islet cell cytoplasm (ICA), glutamic acid decarboxylase(LGAD), and tyrosinphosphatase (IA-2) (Table 1.10). Islet cell autoantibodies can often be detected many years before clinical manifestation. Transient presence of antibodies may have no relevance, but persisting antibodies indicate that type 1 diabetes will follow with a probability that increases if more than one autoantibody is detected and if they are present at high titers. In antibody-positive persons they should be monitored once or twice per year. Tests for insulin secretory capacity may have additional predictive value [44].
At manifestation symptoms are more frequent in younger than in older individuals. In young subjects it may be only hours or a few days from the first signs until a serious clinical syndrome develops. In later adulthood, the progression from insulin deficiency to overt clinical diabetes is often retarded [120–122]. The clinical picture of these people may resemble that of type 2 diabetes, but they are islet cell antibody-positive and will usually need insulin during the first year after diagnosis. It can be expected that about 10% of newly diagnosed diabetic subjects originally classified as having type 2 in fact have this form of type 1 diabetes [12]. The term “latent autoimmune diabetes inadults” (LADA) has been used to describe this subgroup.
Table 1.10 Islet cell specific autoantibodies in type 1 diabetes. Prevalence at manifestation
| Antibodies to | Prevalence (%) |
|---|---|
| Islet cell cytoplasm (ICA, IgICA, ICCA) | 60-90 |
| Glutamic acid decarboxylase (GAD) | 70-90 |
| IA-2 | 70-90 |
| IA-2β | >50% |
| Insulin (IAA) | 20-100 |
| Proinsulin (PAA) | 10-20 |
| BSA | 60-100 |
| ICA 69 | 60 |
| 38-kDa insulin granules | > 30 |
| Glucose transporter | 80-100 |
| Carboxy peptidase H | 30-50 |
| Polar antigen | 30-50 |
| 52-kDa protein | > 30 |
| 150-kDa protein | 80-100 |
| Islet cell surface (ICSA) | 60-80 |
Adapted from [120]
Frequently the manifestation of type 1 diabetes seems to be precipitated by coincident diseases that increase the insulin requirement, such as infections, pregnancy, hyperthyroidism, glucocorticoid treatment, or severe somatic stress (myocardial infarction, major surgery, etc,).
In about two-thirds of subjects a remission will follow the initiation of therapy. The required insulin dose decreases and metabolism stabilizes due to some recovery of insulin and C-peptide secretion together with improved insulin sensitivity. The remission period can be prolonged by experimental immunomodulatory therapy [123]. However, sooner or later the individual will become C-peptide-negative. After some weeks or months, remission is usually followed by a relapse and the development of irreversible clinical diabetes, which under unfavorable conditions may proceed to end-stage diabetes with chronic complications.
If diabetes mellitus is suspected, the diagnosis should immediately be checked by laboratory tests. If the diagnosis is confirmed, it is advisable to start therapy and normalize the metabolism promptly, because this seems to improve the chances of inducing a remission [124].
Treated type 1 diabetes mellitus is not associated with hypertension, lipid disorders, or obesity. However, this does not rule out their existence at diagnosis or that they may develop later. The further course of the disease is determined by the lability of the metabolism, problems of insulin substitution, glucose monitoring, hypoglycemia, and hyperglycemia. The quality of metabolic control is the main determinant of the prognosis.
Type 2 Diabetes
In the majority of cases the disease begins as a metabolic syndrome. In this early stage most symptoms are reversible. Progression to clinical diabetes is not inevitable. The progress of the blood glucose disorder from impaired fasting glucose or impaired glucose tolerance to overt diabetes may take years. Even when diagnostic criteria are reached, hyperglycemia may not cause the classical symptoms, and glucosuria may be minimal or lacking due to an elevated renal threshold. Other symptoms will often be misinterpreted as a normal attribute of aging. Thus, it may take a couple of years until diabetes is diagnosed.
In contrast to type 1 diabetes mellitus, glucose metabolism in type 2 diabetes mellitus is usually fairly stable. However, treatment is usually more difficult than in type 1 diabetes because it requires life-style changes. The disorder tends to increasing severity, and over the years it becomes more and more difficult to achieve near-normal metabolic control [125]. As in the case of type 1 diabetes, the prognosis of type 2 diabetes depends on the quality of metabolic control. However, in addition to glucose metabolism, the other components of the metabolic syndrome such as obesity, hypertension, and dyslipoproteinemia, and life style are equally important.
The chronic complications of diabetes - mainly microangiopathy, neuropathy, and macroangiopathy - are major problems, because they determine the prognosis and quality of life of the patients. Although the details of their pathogenesis are not fully understood, there is no doubt that the diabetic condition is the major cause. Epidemiological studies have shown that their incidence increases with poor metabolic control [126–132] and can be reduced by lowering HbA1c[127,130,131,133]; however, the beneficial effect of strict metabolic control on macroangiopathy is rarely significant [127,130,133–135]. Many proposals have been put forward to explain “diabetes the risk factor,” which forms a network of potentially pathogenetic mechanisms. Recent articles have covered specific topics and the reader is referred to these publications [136–145]. It is not the aim of this short introduction to add another review.
In addition to insulin deficiency/hyperglycemia. other pathogenic factors such as adverse life style, hypertension, lipid disorders, proteinuria, unfavorable hemorrheology, and activated hemostasis are also involved. These will be mentioned in the context of the various clinical manifestations.
The following section outlines the role of hyperglycemia in the pathogenetic network leading to microangiopathy [146–149].
