Impaired glucose tolerance (prediabetes) is defined as: 1.
A fasting plasma glucose between 100 and 125 mg/dL (“impaired fasting glucose”), and/or 2.
during an oral glucose tolerance test, and/or 3. HbA1C level between 5.7% and 6.4%
As many as one-fourth of individuals with impaired glucose tolerance will develop overt diabetes in the next 5 years, with additional risk factors such as obesity and family history compounding such risk. In addition, individuals with prediabetes have an elevated risk of cardiovascular disease.
Although all forms of diabetes share hyperglycemia as a common feature, the underlying causes of hyperglycemia vary widely. Previous classification schemes of diabetes were based on age at onset of the disease http://ebooksmedicine.net
Table20.5SimplifiedClassificationofDiabetes 1.
Type 1 Diabetes Betacelldestruction,usuallyleadingtoabsoluteinsulindeficiency 2.
3.
Genetic Defects of Beta Cell Function Maturity-onsetdiabetesoftheyoung(MODY)(seetext)Insulingenemutations 4.
5.
6.
7.
8.
9.
ModifiedfromDiagnosisandclassificationofdiabetesmellitus(AmericanDiabetesAssociation).Diabetes Care 37:S81-S90;2014.
or on the mode of therapy; in contrast, the current etiologic classification reflects a greater understanding of the pathogenesis of each variant (
Table 20.5 ). The vast majority of cases of diabetes fall into one of two broad classes:
Type 1 diabetes is an autoimmune disease characterized by pancreatic β-cell destruction and an absolute deficiency of insulin. It accounts for approximately 5% to 10% of all cases, and is the most common subtype diagnosed in patients younger than 20 years of age.
Type 2 diabetes is caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic β cells (“relative insulin deficiency”). Approximately 90% to 95% of diabetic patients have type 2 diabetes, and many of them are overweight. Although classically considered “adult-onset,” the prevalence of type 2 diabetes in children and adolescents is increasing at an alarming pace due to the increasing rates of obesity in these age groups.
A variety of monogenic and secondary causes are responsible for the remaining cases (discussed later). Of note, when combined, monogenic and secondary forms of diabetes account for >10% of diabetes (which together makes them more common than type 1 diabetes). An important point is that although the major types of diabetes arise by different pathogenic mechanisms, the long-term complications in kidneys, eyes, nerves, and blood vessels are the same and are the principal causes of morbidity and death.
Before discussing the pathogenesis of the two major types of diabetes, we briefly review normal insulin physiology and glucose metabolism.
Normal glucose homeostasis is tightly regulated by three interrelated processes: (1) glucose production in the liver; (2) glucose uptake and utilization by peripheral tissues, chiefly skeletal muscle; and (3) the actions of insulin and counterregulatory hormones (especially glucagon).