Longterm Complications

T1D may ultimately lead to such dreadful conditions as blindness, limb amputations, and renal failure calling for dialysis or renal transplantation. Hence, for both patients and health care workers prevention and delay of long-term complications are important incentives in striving for good glycemic control. Long-term complications in type 1 diabetic patients (see Table 3) are traditionally divided into microvascular complications, comprising retinopathy, nephropathy, and neuropathy, and macrovascular damage, including peripheral vascular disease (PVD), coronary artery disease (CAD), and cerebral vascular disease (CVD). Moreover, musculoskeletal complications and the diabetic foot are clinical entities that are multicausal and/or for which causes are not yet fully understood. Long-term complications are prevalent in any population of type 1 diabetic patients with increasing prevalence and severity in relation to disease duration and glycemic control and other risk factors.

Table 3

Overview of long-term complications and associated conditions of type 1


Microvascular Retinopathy

Neuropathy Nephropathy

Macrovascular (atherosclerosis) Coronary heart disease (CHD)

Peripheral vascular disease (PVD) Cerebral vascular disease (CVD) Diabetic foot (multi causal)

Co -existing risk factors for atherosclerosis Hypertension

Dyslipidemia Smoking Obesity Family history

Miscellaneous Musculoskeletal

Diabetic foot (multicausal)

Although clinicians and scientists believed for decades that the level of glycemic control is crucial for the risk of future complications, it was not until 1993 before the publication of the first randomized-controlled trial (widely known as the diabetes control and complications trial (DCCT)) which supplied evidence that better glycemic control is actually able to reduce the risk of microvascular complications, making intensive insulin treatment worthwhile (21). A follow-up study (the Epidemiology of

Diabetes Interventions and Complications (EDIC) study) showed comparable results for macrovascular sequelae (22).

The pathogenesis of diabetic complications is multifactorial, complicated, and not yet fully elucidated. In brief, focusing on the role of hyperglycemia, so-called advanced glycation end products (AGEs) and sorbitol are considered to contribute to tissue damage. In addition there may be more tissue-specific factors that contribute to tissue damage, like protein kinase C in the kidney. An overview of current insights into the pathogenesis of long-term diabetic complications is supplied by Michael Brownlee (23).


Diabetic retinopathy is the most widespread cause of visual loss in the Western world and probably the most feared complication of diabetes. It is caused by microangiopathic lesions of the retinal precapillary arterioles, capillaries, and venules. Damage is caused both by microvascular leakage from breakdown of the inner blood-retinal barrier and by microvascular occlusion.

Prevalence of retinopathy at 8-10 years after the onset of diabetes in more recent reports varies between 30 and 60%. This is lower than may be expected from older cohort studies. Data support the conclusion that this may be attributed to better levels of glycemic control that are achieved during the last decades (24). It was already known from previous intervention studies that the development and progression of diabetic retinopathy in T1D can be prevented by better glycemic control (25). An important observation from these trials is that retinopathy may actually worsen during the first year of tightened glycemic control. This observation is even more relevant with respect to women planning to become pregnant: this usually calls for intensified insulin treatment in order to achieve adequate glycemic control before conception. Although the risk of progression during pregnancy is increased in women with the highest initial HbAlc values and in those with the greatest reduction in HbAlc values, probably factors related to pregnancy per se also contribute. Apart from glycemic control other factors that increase the risk of, or are associated with, retinopa-thy include diabetes duration, albuminuria and nephropathy, and hypertension. Lowering blood pressure has been shown to decrease the progression of retinopathy in type 2 diabetes. Epidemiological data suggest that the same is probably true for T1D.

Several systems for the classification of the severity of diabetic retinopa-thy and diabetic macular edema exist. An international group of experts reached consensus about a five-stage disease severity classification that was developed for clinical purposes aiming to improve screening of people with diabetes and in order to facilitate proper communication and discussion among health care providers (Table 4) (26).

Table 4

Diabetic retinopathy (DR) disease severity scale1

Table 4

Diabetic retinopathy (DR) disease severity scale1

Severity level ofDR

Ophthalmoscopic findings

No apparent retinopathy

No abnormalities

Mild nonproliferative

Microaneurysms only

Moderate nonproliferative

More than just microaneurysms but less than

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