Glycaemic control

It should be remembered that some of the established antioxidants have other metabolic roles apart from free-radical scavenging. The finding of reduced antioxidant defences in diabetes, for example, may not be prima fascie evidence of increased oxidative stress, since alternative explanations may operate. For example, this may reflect a response to reduced free-radical activity as su ested by the results of a previous study (Collier et al., 1988). In the case of ascorbate, an alternative explanation has been proposed by Davis etal. (1983), who demonstrated competitive inhibition of ascorbate uptake by glucose into human lymphocytes. This view is supported by the similar molecular structure of glucose and ascorbic acid (see Fig. 12.4) and by a report of an inverse relationship between glycaemic control and ascorbate concentrations in experimental diabetes in rats. Other investigators, however, have not demonstrated this relationship (Som etal., 1981 Sinclair etal., 1991). 

Pre-approval safety and efficacy clinical studies involved product administration to 2500 adults with either type-1 or -2 diabetes. The primary efficacy parameter measured was glycaemic control (as measured by the reduction from baseline in haemoglobin Ale). Hypoglycaemia was the most commonly reported adverse effect. Trials also showed a greater decline in pulmonary function in the Exubera group, and product should not be administered to patients with underlying lung disease, or to smokers. Exubera was developed by Nektar Inc. and is marketed under licence by Pfizer. 

If the findings relating to obesity and improved glycaemic control can be confirmed in human studies such drugs would be highly attractive. As discussed above, bile-acid sequestrants have been used for many years to treat dyslipi-demia in relation to reducing cardiovascular disease risk and the safety profile of these compounds is well established. However, due to the large doses of compound that require to be consumed, compliance is an issue for BAS therapies. In the future, this may be resolved with the development of more specific and efficient resins that require lower doses. 

Although no biopharmaceutical product delivered to the bloodstream via the pulmonary route has been approved to date, several companies continue to pursue active research and development programmes in the area. Amongst the leading product candidates is Exubera , an inhalable dry powder insulin formulation currently being evaluated by Pfizer and Aventis Pharma in Phase III clinical studies. The inhaled insulin is actually more rapidly absorbed than if administered subcutaneously and appears to achieve equivalent glycaemic control. While promising, final approval or otherwise of this product also depends upon additional safety studies which are currently under way. 

Hodgson JM et al Coenzyme Q10 improves blood pressure and glycaemic control A controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002 56 1137. [PMID 12428181]... 

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Weaver JU, Robertson D, Atkin SL, on behalf of the Nateglinide Glycaemic Control Investigators. Nateglinide alone or with metformin safely improves glycaemia to target in patients up to an age of 84. Diabetes Obesity Metab 2004 6 344-52. 

Buysschaert M, Bobbioni E, Starkie M, Frith LTroglitazone Study Group. Troglitazone in combination with sulphonylurea improves glycaemic control in Type 2 diabetic patients inadequately controlled by sulphonylurea therapy alone. Diabet Med 1999 16(2) 147-53. 

Britton ME, Denver AE, Mohamed-Ali V, Yudkin JS. Effects of glimepiride vs glibenclamide on ischaemic heart disease risk factors and glycaemic control in patients with type 2 diabetes mellitus. Clin Drug Invest 1998 16 303-17. 

Wolffenbuttel BH, Gomis R, Squatrito S, Jones NP, Patwardhan RN. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Diabet Med 2000 17(l) 40-7. 

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Reinstein MJ, Sirotovskaya LA, Jones LE, Mohan S, Chasanov MA. Effect of clozapine-quetiapine combination therapy on weight and glycaemic control. Clin Drug... 

Scherbaum WA. Unlocking the opportunity of tight glycaemic control. Inhaled insulin clinical efficacy. Diabetes ObesMetab. 2005 7(suppl 1) S9-S13. 

Bluher M, Unger R, Rassoul F Richter V Paschke R, Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or type II diabetes. Diabetologia 2002 45 210-216. 

Gomis, R, Jones, N. P., Vallance, S. E., and Patwardhan, R. (1999). Low Dose Rosiglitazone Provides Additional Glycaemic Control When Combined with Sul-fonylureas in Type 2 Diabetes (Abstract). Diabetes48, (Suppl. 1), A63. 

Since vesperlysine A was elevated in dogs with moderate glycaemic control, whereas pentosidine, a glycoxidation product, was elevated only in dogs with poor control, the former becomes a unique marker for mild hyperglycaemia.368... 

CM is a 27-year-old white woman with type 1 diabetes diagnosed at age 14 when she presented with diabetic ketoacidosis. Her initial insulin treatment was complicated by poor glycaemic control, frequent hypoglycaemia and weight gain. 

CM was started on intravenous insulin, fluids, and electrolyte replenishment. Her nausea and vomiting resolved and, although initially, she required 60-70 units of insulin intravenously per day to attain glycaemic control, her blood glucose dropped to 7.4 mmol/L after 4 days of intensive care. However, despite treatment of her diabetic ketoacidosis, including significant rehydration therapy, CM was still found to have an elevated but stable serum creatinine of 246 micromol/L, and so she was transferred from the intensive care unit to the renal unit for further management. 

The retina is the most metabolically active tissue in the body and so is very vulnerable to the microvascular changes which occur in diabetes. Diabetes affects the eyes in a number of ways the most common is diabetic retinopathy, which involves increased thickness of the retinal basement membrane and increased permeability of its blood vessels. The severity of the retinopathy is related to the age of the patient, duration of the diabetic state and extent of glycaemic control. Later changes in the eye include macular oedema and retinal ischaemia, which threaten the sight of the patient. All these deleterious changes are minimized if blood glucose is tightly controlled. 

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