Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Direct measurement of the lumped constant for 2-deoxy-[1-(14)C]glucose in vivo in human skeletal muscle

The lumped constant (LC) is used to convert the clearance rate of 2-deoxy-D-glucose (2-DG(CR)) to that of glucose (Glc(CR)). There are currently no data to validate the widely used assumption of an LC of 1.0 for human skeletal muscle. We determined the LC for 2-deoxy-[1-(14)C]glucose (2-DG) in 18 normal male subjects (age, 29+/- 2 yr; body mass index, 24.8+/-0.8 kg/m(2)) after an overnight fast and during physiological (1 mU x kg(-1) x min(-1) insulin infusion for 180 min) and supraphysiological (5 mU x kg(-1) x min(-1) insulin infusion for 180 min) hyperinsulinemic conditions. Normoglycemia was maintained with the euglycemic clamp technique. The LC was measured directly with the use of a novel triple tracer-based method. [3-(3)H]glucose, 2-[1-(14)C]DG, and [(12)C]mannitol (Man) were injected as a bolus into the brachial artery. The concentrations of [3-(3)H]glucose and 2-[1-(14)C]DG (dpm/ml plasma) and of Man (micromol/l) were determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein over 15 min after the bolus injection. The LC was calculated by a formula involving blood flow calculated from Man and the Glc(CR) and 2-DG(CR). The LC averaged 1.26+/-0.08 (range 1.06-1.43), 1.15+/-0.05 (0.99-1.39), and 1.18+/-0.05 (0.97-1.37) under fasting conditions and during the 1 and 5 mU x kg(-1). min(-1) insulin infusions (not significant between the different insulin concentrations, mean LC = 1.2, P<0.01 vs. 1.0). We conclude that, in normal subjects, the LC for 2-DG in human skeletal muscle is constant over a wide range of insulin concentrations and averages 1. 2