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Oral presentation

Diabetes is epidemic and still one of the most growing diseases worldwide. Type 2 diabetes accounts for approximately 90% - 95% of all cases with a year 2001 prevalence ranging in industrialized countries between 2.7% (France) and 5.8% (USA) [1]. Acute symptoms of diabetes include polyuria, polydipsia, weight loss, and random or fasting blood glucose concentrations ≥ 11.1 mmol/L (200 mg/dL) and ≥ 7.0 mmol/L (126 mg/dL), respectively. From a pathophysiological perspective, type 2 diabetes is characterized by resistance to insulin action, inadequate compensatory insulin secretory response, or both.

The condition is still frequently under-diagnosed: current diagnostic rates are at maximum 75% and it requires on average 7 years after the onset of disease until a type 2 diabetic patient is diagnosed, a time during which the disease is not benign.

Type 2 diabetes is a complex and serious disease [2]. A high proportion of patients are at increased risk for devastating microvascular and macrovascular complications. As such type 2 diabetes is the leading cause of adult blindness [3], the leading cause of end stage renal disease [4], the leading cause of non-traumatic lower limb amputations [5], and increases the overall cardiovascular mortality up to 6-fold [6].

Type 2 diabetes is a progressive disease. Regardless of therapeutic intervention, glucose control deteriorates progressively over time. After failure of diet and exercise alone, on average every 3-4 years a new intervention with an additional glucose-lowering agent is required to maintain or retain good blood glucose control. In spite of combination therapy and / or insulin treatment an important group of patients is not well controlled [2].Type 2 diabetes is further frequently associated with hypertension, dyslipidemia and obesity, a symptom-complex denoted 'syndrome X' or 'metabolic syndrome' [7]. Due to this, type 2 diabetic patients are usually subject to multi-drug therapy, predominantly consisting of various oral antidiabetic drugs (sulfonylureas, biguanides, thiazolidinediones,α-glucosidase inhibitors, and meglitinides), insulin or insulin-analogues, anti-hypertensives, lipid-lowering agents, and anti-obesity drugs.What makes the diabetic population in particular special in the overall context of drug development, however, is the frequent presence of diabetic gastroparesis (in broader terms diabetic gastro-enteropathy), which is probably the most common single clinical condition which causes chronically delayed gastric emptying. Gastroparesis affects both type 1 and type 2 diabetic patients. It is well recognized that delayed gastric emptying in diabetes results in inconsistent and erratic absorption of carbohydrate and poor glycaemic control, and ultimately in further progression of the chronic disease complications. Although it is generally well acknowledged that the rate of gastric emptying is also a major determinant of the rate and extent of drug absorption, inappropriately, the impact of diabetic gastroparesis on the bioavailability and pharmacokinetics of orally administered drugs has received little attention in the past. The presentation will review the scarce information in that regard and will highlight issues, which should be addressed for development compounds, which are intended to be used in diabetic patients. The presentation also attempts to address various practical points to consider for study planning and conduct in the population of diabetic patients.

References

1. Harris MI: Early detection of undiagnosed diabetes mellitus: a US perspective.

   Diabetes Metabolism Research and Reviews 2000, 16:230-36. PubMed Abstract | Publisher Full Text

2. The European Agency for the Evaluation of Medicinal Products: Note for Guidance on Clinical Investigation of Medical Products in the Treatment of Diabetes Mellitus. CPMP/EWP/1080/00. May 30, 2002
3. World Health Organisation [WHO] Fact Sheet N114. Feb 1997
4. Harris MI, et al.:

   Diabetes in America 2 Edition Washington, DC: National Institutes of Health 1995.

5. Wingard DL, et al.:

   Diabetes in America2 Edition 1995.

6. Kuller LH, et al.:

   Diabetes in America2 Edition 1995.

7. Reaven GM: Syndrome X: six years later.

   J Int Med 1994, 236(Suppl):13-22.

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