Type 2 diabetes accounts for more than 90% of all diabetes cases and affects 10% to 20% of the adult populations of many high-income countries. Several features distinguish it from type 1 diabetes.
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There is always some endogenous insulin production in people with type 2 diabetes, and the disease is often treated successfully with dietary modification and/or oral drugs.
People with type 2 diabetes suffer from insulin resistance (i.e., their cells have difficulty in using insulin).
This disease typically occurs among people older than age 40 and, in contrast to type 1 diabetes, is more common among the obese.
The incidence of type 2 diabetes is rising dramatically among adolescents and young adults in developed countries and is strongly correlated with an increased incidence of obesity.
Neither MHC associations nor autoantibodies are commonly seen in this form of diabetes.
MZ twin concordance rates are substantially higher than those seen in type 1 diabetes, ranging from 70% to 90% (because of age dependence, the concordance rate increases if older subjects are studied).
The empirical recurrence risks for first-degree relatives of type 2 diabetes cases are higher than those for type 1, generally ranging from 15% to 40%.
The table outlines the differences between type 1 and type 2 diabetes.
Table 5.5 Comparison of Major Features of Types 1 and 2 Diabetes
Feature
Type 1 Diabetes
Type 2 Diabetes
Age of onset
Usually >40 years
Usually >40 years (except maturity-onset diabetes of the young [MODY])
Insulin production
None
Partial
Insulin resistance
No
Yes
Autoimmunity
Yes
No
Obesity
Not common
Common
Monozygotic (MZ) twin concordance
0.30–0.70
0.35–0.60
Sibling recurrence risk
1%–6%
10%–40%
Studies are undertaken to identify genes that contribute to type 2 diabetes susceptibility, and more than 250 genes and more than 400 genomic variants are now known to be associated with risk of this disease.
The table lists the associations between diabetes susceptibility and each of these genes have been widely replicated in multiple populations.
Genes
Description
TCF7L2
Encodes a transcription factor involved in the secretion of insulin.
Its variant is associated with a 50% increased risk of developing type 2 diabetes.
Allele
Significant association is observed between type 2 diabetes and a common allele of the gene that encodes peroxisome proliferator–activated receptor-gamma (PPAR-γ), a nuclear receptor, involved in adipocyte differentiation and glucose metabolism.
This receptor is the target of thiazolidinediones (TZDs), a class of drugs used to increase insulin sensitivity in those with type 2 diabetes.
The disease-associated allele confers only a 25% increase in the risk of developing type 2 diabetes but, it is found in more than 75% of individuals of European descent.
KCNJ11
Variation in KCNJ11 , which encodes a potassium channel necessary for glucose-stimulated insulin secretion, confers an additional 20% increase in type 2 diabetes susceptibility.
Two most important risk factors for type 2 diabetes are positive family history and obesity; the latter increases insulin resistance.
The disease tends to rise in prevalence when populations adopt a diet and exercise pattern typical of U.S. and European populations.
Increases are seen, example, among Japanese immigrants to the United States and among some native populations of the South Pacific, Australia, and the Americas.
Due to dramatic increase in obesity in the United States and other developed countries, the prevalence of type 2 diabetes is also rising rapidly, and the average age of onset is decreasing (one study estimates that up to one-third of Americans born in the year 2000 will develop type 2 diabetes).
A small proportion of type 2 diabetes cases occurs early in life, often before 25 years of age, and typically exhibits autosomal dominant inheritance (unlike most type 2 diabetes cases). This subset is termed maturity-onset diabetes of the young (MODY).
Studies of MODY pedigrees shows that approximately half of cases of the disease are caused by mutations in the glucokinase gene. Glucokinase converts glucose to glucose-6-phosphate in the pancreas.
In addition to the glucokinase gene, five other genes, are involved in pancreatic development or regulation of insulin levels, are now shown to be causes of MODY. Currently, 13 MODY genes are known.
Studies, conducted on male and female subjects, shows that regular exercise can substantially lower one’s risk of developing type 2 diabetes, even among individuals with a family history of the disease.
This is partly because exercise reduces obesity.
Even in the absence of weight loss, exercise increases insulin sensitivity and improves glucose tolerance.
What is the pathophysiology of type 2 diabetes?
