The ß-cell in impaired glucose regulation - when to initiate the treatment?

A.D.M. Stork
Utrecht, The Netherlands

In Monday’s session on the clinical heterogeneity of diabetes, Dr Bonadonna presented data indicating that impaired glucose regulation, i.e. impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), is associated with both reduced insulin sensitivity and reduced insulin secretion, these defects being most severe in patients with both IFG and IGT.
Dr Van Haeften showed that in the natural course of progression from IFG to Type 2 diabetes, IFG is characterized by a similar reduction in insulin sensitivity to that found in Type 2 diabetes, but with a less pronounced reduction in ß-cell function. This was supported by interesting research from Dr Lev-Ran, who challenged the view that in Type 2 diabetes the endogenous insulin secretion first increases and then decreases with time and is suppressed at higher levels of glycaemia, its curve resembling the Starling curve. By determining C-peptide in 360 patients widely differing in their duration of diabetes and level of fasting glycaemia, he showed that C-peptide neither increases nor decreases with time. In fact, in patients with newly diagnosed diabetes or Type 2 diabetes of more than 20 years’ duration, C-peptide declined by only 11%. This led Dr Lev-Ran to hypothesize that in the years preceding impaired glucose regulation this condition is compensated by chronic maximal insulin secretion of the ß-cells, which persists throughout life in Type 2 diabetic subjects.

Should we initiate treatment before diagnosis of diabetes?
The data presented again support the idea that the process of impaired insulin sensitivity and secretion is put in motion many years before the diagnosis of impaired glucose regulation or Type 2 diabetes, and raises the question whether or not treatment should be initiated much earlier in the course of the disease.
Furthermore, amyloid may play an important role in ß-cell dysfunction. This polypeptide is produced together with insulin and deposited in the ß-cells of most patients with Type 2 diabetes, causing ß-cell failure. Reduction of endogenous insulin production, and thus reduction of amyloid production, may inhibit islet amyloidosis.
It may therefore be beneficial to start treatment targeted at decreasing endogenous glucose production or at increasing insulin sensitivity very early, whereas treatment with sulfonylureas, increasing insulin and hence amyloid production, may have negative effects in the long term. Research is currently being carried out on the early initiation of treatment.


Coexistence of Type 1 and Type 2 diabetes?
During the same session the fascinating concept of the coexistence of Type 1 and Type 2 diabetes was discussed by Dr Damci, presenting research comparing insulin sensitivity, blood pressure, waist circumference and lipid profiles of Type 1 diabetic patients with and without first-degree relatives with Type 2 diabetes.
Type 1 diabetic patients who have first-degree relatives with Type 2 diabetes tend to be more insulin-resistant, have higher systolic and diastolic blood pressures, larger waist circumferences and more dyslipidaemia, all features resembling the metabolic syndrome. It may therefore be possible that in some patients with Type 1 diabetes, Type 2 diabetes coexists.
Why would patients with Type 1 diabetes be spared from the metabolic syndrome? Certainly, ß-cell dysfunction will not play a role in these patients, but insulin resistance and other features of the metabolic syndrome will. This could account for the beneficial effects of metformin in some Type 1 diabetic patients.
It seems advisable to be alert for features of the metabolic syndrome in Type 1 diabetic patients, to treat them aggressively, and also to consider treatment with insulin-sensitizing drugs.

Back to Top