Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.2
A.2. Scientific background and rationale for study elements
area of cerebrovascular diseases as an interdisciplinary field between the cardiovascular
and neurologic-psychiatric disorders.
A.2.2.2 diabetes mellitus
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia with
anomalies in carbohydrate, fat, and protein metabolism caused by defects in insulin secretion,
insulin action, or a combination of the two. Metabolic syndrome and type 2 diabetes
are important risk factors for the development of vascular complications. Life expectancy is
substantially reduced in patients with impaired glucose tolerance and type 2 diabetes, and
more than 75% die from macrovascular complications such as MI or stroke (see the section
on CVD). Peripheral arterial disease (PAD) and/or diabetic neuropathy are common causes
of diabetic gangrene, resulting in more than 35,000 amputations per year in patients with
type 2 diabetes in Germany. Diabetes is a major cause of severe microvascular complications
such as end-stage renal disease or diabetic retinopathy with the risk of blindness. In
addition, diabetes and prediabetic states are also established risk factors for cancers of
different sites, including colon, endometrium, and pancreas 54 . The worldwide prevalence of
diabetes was estimated to be 220.5 million in 2004 55 and numbers are projected to increase
to 366 million by 2030. In Germany, diabetes mellitus is among the most common diseases
with about 6 million patients and an equal number of undiagnosed cases or persons at high
risk probably exist 56, 57 .
Type 2 Diabetes: The by far most frequent form of diabetes is type 2, and this type is the
major component of the worldwide diabetes epidemic 58 . Therefore, it is crucial to understand
the etiology of type 2 diabetes, and the development of preventive strategies for
this disease is a key public health target. Among the major, established causes of type 2
diabetes are excess body weight, lack of physical activity, and an unhealthy diet; intervention
trials have shown that in high-risk individuals with impaired glucose tolerance the risk
of progression to diabetes can be drastically reduced through lifestyle interventions such
as weight reduction, dietary changes, and increased physical activity, or by drug therapy
with metformin or acarbose 59-64 . One of the major challenges that still must be resolved,
however, is to determine the best strategies for identifying high-risk individuals and those
subjects who would benefit most from specific intervention strategies.
Often, type-2 diabetes takes several decades to develop, including a process with different
stages of prediabetes, eventually resulting in a clinical diagnosis. The decisive event at the
end of this process is the progressive failure of beta-cell function. The pathological mechanisms
leading to diabetes may vary between individuals. According to current knowledge,
different pronounced pathomechanisms are relevant and different organs (e.g., liver, fat
tissue, heart, or brain) may take a leading role. Based on current research findings in the
field of diabetes genetics and the expected results arising from other –omics technologies,
especially metablomics, proteomics, and epigenomics, we will be able to refine the definition
of subphenotypes of type 2 diabetes. By identifying such subphenotypes, new ways will
be opened to understand the interactions between genetic background, metabolism, and
lifestyle factors in the development of type 2 diabetes. In combination with the large sample
size and precise data on physical activity, body composition, etc., as well as information on
the utilization of health care, the National Cohort will offer unique opportunities for studies
on diabetes etiology, individualized diabetes prediction and prevention, treatment of diabetes
and diabetes complications, also considering quality-of-life aspects among diabetic
patients and economic consequences for the health care system.
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