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Glycemic control and vascular complications in type 1 diabetes mellitus

Author
David K McCulloch, MD
Section Editor
Irl B Hirsch, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Morbidity from diabetes is a consequence of both macrovascular disease (atherosclerosis) and microvascular disease (retinopathy, nephropathy, and neuropathy). Epidemiologic studies first showed an association between poor glycemic control and microvascular complications [1-4]. The causal relationship of this association was confirmed in the prospective Diabetes Control and Complications Trial (DCCT), which demonstrated that intensive therapy aimed at lower levels of glycemia results in decreased rates of retinopathy, nephropathy, and neuropathy in type 1 diabetes patients [5,6]. Similar findings have been noted in other studies [7].

The importance of tight glycemic control for protection against macrovascular disease in diabetes has also been established in the DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) study for type 1 diabetes. In the EDIC follow-up study to the DCCT, intensive insulin therapy in patients with type 1 diabetes decreased fatal and nonfatal cardiovascular events [8]. The effects of glycemic control on microvascular and macrovascular complications in type 1 diabetes will be reviewed here. Glycemic control and vascular complications in type 2 diabetes is discussed separately. (See "Glycemic control and vascular complications in type 2 diabetes mellitus".)

PATHOGENESIS

The mechanism by which lack of glycemic control predisposes to vascular disease is incompletely understood. Two proposed contributing factors are advanced glycation end products and sorbitol; protein kinase C and other factors also may contribute (algorithm 1). In addition to systemic factors, organ-specific factors also appear to be important. In the kidney, for example, stimulation of mesangial matrix production by hyperglycemia, activation of protein kinase C, and an increasing degree of intraglomerular hypertension may contribute to the glomerular injury. (See "Protein kinase C and the vascular complications of diabetes mellitus".)

Genetic predisposition may be another important factor. This was illustrated in a report from the Diabetes Control and Complications Trial (DCCT) in which 372 patients and 467 first-degree relatives with diabetes were evaluated [9]. Severe retinopathy was three times more frequent among the relatives of patients with retinopathy than among relatives of patients who did not have retinopathy. Familial clustering was also noted for diabetic nephropathy.

A more in-depth discussion of the pathogenesis of diabetic nephropathy, retinopathy, and neuropathy can be found elsewhere. (See "Overview of diabetic nephropathy", section on 'Pathogenesis' and "Diabetic retinopathy: Pathogenesis" and "Pathogenesis and prevention of diabetic polyneuropathy", section on 'Pathogenesis'.)

                  

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Literature review current through: Nov 2016. | This topic last updated: Mon Oct 31 00:00:00 GMT+00:00 2016.
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