Genetics and Diabetes
Background
Diabetes mellitus is a heterogeneous group of disorders characterized by persistent hyperglycemia.
The two most common forms of diabetes are type 1 diabetes (T1D, previously known as insulin-
dependent diabetes or IDDM) and type 2 diabetes (T2D, previously known as non-insulin-dependent
diabetes or NIDDM).
Both are caused by a combination of genetic and environmental risk factors.
However, there are other rare forms of diabetes that are directly inherited.
These include maturity
onset diabetes in the young (MODY), and diabetes due to mutations in mitochondrial DNA.
All forms of diabetes have very serious effects on health.
In addition to the consequences of abnormal
metabolism of glucose (e.g., hyperlipidemia, glycosylation of proteins, etc.), there are a number of
long-term complications associated with the disease.
These include cardiovascular, peripheral
vascular, ocular, neurologic and renal abnormalities, which are responsible for morbidity, disability and
premature death in young adults.
Furthermore, the disease is associated with reproductive
complications causing problems for both mothers and their children.
Although improved glycemic
control may decrease the risk of developing these complications, diabetes remains a very significant
cause of social, psychological and financial burdens in populations worldwide.
Type 1 Diabetes
Epidemiology
.
T1D is caused by the autoimmune destruction of the beta cells of the pancreas, and
represents approximately 10% of all cases with diabetes.
At present, lifelong insulin therapy is the only
treatment for the disease.
Without exogenous insulin injections, individuals with T1D will not survive.
Although the prevalence of T1D is <1% in most populations, the geographic variation in incidence is
enormous, ranging from <1/100,000 per year in China to approximately 40/100,000 per year in Finland
(Figure 1) (Karvonen et al., 1993).
The only chronic childhood disorder more prevalent than T1D is
asthma.
It has been estimated that approximately 20 million people worldwide, mostly children and
young adults, have T1D (Holt, 2004).
Figure 1.
T1D Incidence Rates Worldwide
0
5
10
15
20
25
30
35
40
FIN
SAR
SWE
NOR
US-WI
US-PA
ITA
ISR
JAP
CHI
/100,000/yr
FIN = Finland, SAR = Sardinia, SWE = Sweden, NOR = Norway, US-WI = US-Wisconsin, US-PA =
US-Pennsylvania, ITA = Italy, ISR = Israel, JAP = Japan, CHI = China
The incidence of T1D is increasing worldwide at a rate of about 3% per year (Onkamo et al., 1999).
This trend appears to be most dramatic in the youngest age groups, and is completely unrelated to the
current increase in T2D in children.
More children with beta cell autoantibodies, a hallmark of T1D,
are being diagnosed with the T1D around the world each year.
Although the peak age at onset is at
puberty, T1D can also develop in adults.
Epidemiologic studies have revealed no significant gender
differences in incidence among individuals diagnosed before age 15 (Kyvik et al., 2004).
However,
after age 25, the male to female incidence ratio is approximately 1.5.
There is also a notable seasonal
