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		Literature Compendium

Current Concepts in Type 2 Diabetes

Volume 1
Overview of Type 2 Diabetes Pathogenesis, Complications, Risk Reduction, and Lifestyle Intervention

Chapter 3
Risk Reduction: The Imperative for Tight Glycaemic Control

Chapter 2 provided an overview of the complications that may develop in people with Type 2 diabetes who do not achieve good glycaemic control. The inevitable occurrence of microvascular and macrovascular complications and increased risk of death provide a sound rationale for making optimal glycaemic control a primary therapeutic goal. Further impetus for this therapeutic approach comes from intervention trials that show objectively the benefits of tight glycaemic control, which include reduction in overall cardiovascular risk and delayed onset of complications. In particular, intensive insulin therapy may be the optimal therapeutic choice to achieve tight glycaemic control and reduce the devastating complications of Type 2 diabetes.

The landmark United Kingdom Prospective Diabetes Study (UKPDS) compared the effect of intensive glycaemic control versus conventional treatment (dietary modification) on the risk of complications in individuals with newly diagnosed Type 2 diabetes.¹ A total of 3867 individuals aged 48 to 60 years were randomized to receive either intensive glycaemic control with a sulfonylurea or insulin or conventional treatment with dietary modification. Intensive treatment substantially decreased the risk of microvascular modifications. This landmark trial provided the strongest evidence to date that tight glycaemic control in individuals with Type 2 diabetes will reduce complications of the disease.

Wright and colleagues² evaluated rates of and contributing factors to hypoglycaemia in a separate population of 5063 UKPDS participants with Type 2 diabetes randomized to insulin therapy, intensive oral treatment (sulfonylurea or metformin if overweight), or diet. Overall, grade 2 to 4 hypoglycaemia was reported by 2.5% of individuals, and grade 3 to 4 hypoglycaemia by 0.55%. Hypoglycaemia was significantly more common in those who were younger, female, or of normal body weight, had a lower HbA_1c, or were islet autoantibody-positive. The investigators concluded that the low rates of hypoglycaemia observed during the first 6 years of intensive insulin therapy are not likely to exert a major impact on attempts to achieve guideline glycaemic targets in individuals with Type 2 diabetes.

Mulcahy and colleagues³ performed a long-term prospective cohort study to determine whether evidence-based targets for glucose level, total cholesterol concentration, and blood pressure could be achieved and sustained in a community hospital setting with tight glycaemic control, statin therapy, and anti-hypertensive therapy. About 25% of individuals studied had Type 1 diabetes. In a pooled analysis of changes from baseline in the entire cohort (n=1516), HbA_1c fell significantly, with commensurate changes in total cholesterol and the proportion of individuals who were normotensive. Over the observation period, insulin use increased from 42% to 72%, metformin use increased from 35% to 55%, statin used increased from 12% to 84%, and anti-hypertensive therapy increased from 52% to 94%. This study demonstrated that it is possible to achieve results similar to those observed in the UKPDS in a real-word practice setting.

Ohkubo and colleagues⁴ evaluated whether tight glycaemic control achieved with intensive insulin therapy in individuals with Type 2 diabetes could decrease the frequency or severity of diabetes-related microvascular complications. In this 6-year trial, 110 individuals with Type 2 diabetes were randomized to receive either conventional insulin treatment or a multiple insulin injection regimen. Retinopathy developed in 7.7% of individuals in the intensive-treatment group, compared with 32.0% of those in the conventional-treatment group (P=0.039). In a secondary cohort, retinopathy developed in 19.2% and 44.0% of individuals in these groups, respectively (P=0.049). Similar results were observed for the development and progression of nephropathy and neuropathy.

Together, these reports provide a strong evidence base for the use of tight glycaemic control as a means of reducing the risk of complications in people with diabetes. Moreover, tight glycaemic control can be achieved without imposing an unacceptable risk of hypoglycaemia.

References 

1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.

2. Wright AD, Cull CA, Macleod KM, Holman RR, for the UKPDS Group. Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73. J Diabetes Complications. 2006;20:395-401.

3. Mulcahy MP, Emmanuel J, Gable D. Sustained glycaemic, lipid and blood pressure control over 6 years in a large outpatient cohort using a repeatedly implemented aggressive treatment protocol. Presented at: 67th Scientific Sessions of the American Diabetes Association; June 22-26, 2007; Chicago, IL. Abstract 531-P [as reprinted in the WorldWIDE Literature Compendium Volume 1].

4. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103-117.

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The Literature Compendium is funded by an educational grant from Pfizer Inc.

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