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Introduction to the 1st International Diamicron® Symposium in Canada
Diabetes Research and Clinical Practice, 14 (1991)Sl-S2 0 1991 Elsevier Science Publishers
DIABET
Sl
B.V. 0168-8227/91/$03.50
00564
Introduction
to the 1st International Diamicrona Canada
Symposium in
J. Mirouze Montreal,
Mr. President,
Moderators,
September
24, 1990
Colleagues,
It is both a real pleasure and an immense honor for me to present and introduce the 1st International Diamicrona Symposium in Canada. Introducing and presenting the symposium means making a rapid summary of non-insulin-dependent diabetes mellitus (NIDDM) and also stating very clearly all that is known about gliclazide or Diamicrone, well-known in France for almost twenty years. While insulindependent diabetes mellitus (IDDM) is increasingly well understood, little progress is being made in our understanding of the apparently more benign NIDDM, which is less severe but more deceptive. NIDDM associates hyperglycemia with hyperinsulinemia and insulin resistance. It is known that hyperinsulinemia precedes glucose intolerance, the increase in blood glucose, and the onset of diabetes: observations frequently gleaned from obese patients and those much less frequently made in patients with acanthosis nigricans associated with polycystic ovaries and hypertrichosis have demonstrated this sequence of events and thus confirmed the existence of insulin resistance. But does hyperinsulinemia precede and insulin resistance follow, or is it the reverse phenomenon which takes place? Insulin resistance has been clearly demonstrated in vitro (by analyzing the number of receptors, postreceptors and kinase activity) and in vivo (using clamp techniques), and it is just as evident in hepatocytes and myocytes. Overproduction of glucose by the liver usually has even more effect when it coexists with hyperinsulinemia. Insufficient binding of glucose to the muscles is partially related either to deficient glucose transport and/or to reduced activity of glycogen synthetase, explaining the deficiency of glycogen in the muscles, and of pyruvate dehydrogenase activity, decreasing the oxidation of glucose. Genetic studies have shown that insulin resistance is in many circumstances a genetically acquired defect. Does hyperinsulinemia, both absolute and relative, result from an anomaly in the insulin gene, insulin receptors, glucose transport, or in receptors for apolipoproteins and LDL? The exact mechanism has not yet been clarified, but each explanation remains plausible. Moreover, hyperinsulinemia is not the only secretory abnormality of NIDDM, and it appears that its association with erythrocyte sodium/lithium cotransport activity increases the risk of hypertension and nephropathy. The same is true of the increase in plasma endothelin and in the inhibitor of plasminogen activity. Levels of amylin, a peptide isolated from insular amyloid deposits, are increased in obese patients who are glucose intolerant or who have NIDDM, and levels show a good correlation with the degree of insulinemia. Amylin is not detectable in IDDM.
s2 While the pathophysiology thanks
to more suitable
of NIDDM
still remains
diets and ever increasing
poorly
defined,
improvements
most of the anomalies in insulin resistance, insulin secretion, ances. I would like to tell you about one such drug, gliclazide
its treatment
continues
to improve
in drugs which are capable
and associated or Diamicrons.
of correcting
endocrine-metabolic
disturb-
Gliclazide or Diamicrons normalizes the physiological insulin response after stimulation by glucose. It also restores the early peak of insulin secretion in the oral glucose tolerance test and increases total insulin secretion, while avoiding hyperinsulinism which might be harmful. Gliclazide controls blood glucose levels not simply by acting on insulin secretion but also by partly correcting insulin liver and even more so in the muscles where it stimulates glycogen synthetase. Gliclazide specific
actions
on small blood
vessels,
their endothelial
secretion
and on blood
resistance in the also has various
platelets.
In particular,
it corrects the decrease in plasma fibrinolytic activity, perhaps via the inhibitor of plasminogen. corrects excessive platelet aggregation and adhesiveness, and reduces the increased thrombotic of diabetics. This is the information that physicians need to have about NIDDM and gliclazide.
It also activity
It is not my role to introduce the twelve speakers who will take turns to tell us all the latest details concerning gliclazide: this will be done by the six moderators who. will come two by two to this platform throughout the afternoon. At this point in my introduction I would like you to remember this old Chinese proverb: ‘When you drink water, think of the source’. In fact, the source is Servier Laboratories with its President and Chief Executive Officer, Dr. Jacques Servier. In France we are very proud of this large pharmaceutical company which is considered one of the most important in our country. Its research laboratories keep it in the forefront of progress and it has recently been ranked first among world pharmaceutical companies for innovation. Gliclazide itself was developed at Servier Research Laboratories, fully justifying our meeting here today in Montreal. In expressing on your behalf all my thanks to the President and Chief Executive Officer of Servier Laboratories, I am also addressing who have played a very important role in ensuring that this antidiabetic could finally the Canadian market. I hope that Diamicronm will have a long and brilliant career.
myself to all those be introduced onto
DIABET
Sl
B.V. 0168-8227/91/$03.50
00564
Introduction
to the 1st International Diamicrona Canada
Symposium in
J. Mirouze Montreal,
Mr. President,
Moderators,
September
24, 1990
Colleagues,
It is both a real pleasure and an immense honor for me to present and introduce the 1st International Diamicrona Symposium in Canada. Introducing and presenting the symposium means making a rapid summary of non-insulin-dependent diabetes mellitus (NIDDM) and also stating very clearly all that is known about gliclazide or Diamicrone, well-known in France for almost twenty years. While insulindependent diabetes mellitus (IDDM) is increasingly well understood, little progress is being made in our understanding of the apparently more benign NIDDM, which is less severe but more deceptive. NIDDM associates hyperglycemia with hyperinsulinemia and insulin resistance. It is known that hyperinsulinemia precedes glucose intolerance, the increase in blood glucose, and the onset of diabetes: observations frequently gleaned from obese patients and those much less frequently made in patients with acanthosis nigricans associated with polycystic ovaries and hypertrichosis have demonstrated this sequence of events and thus confirmed the existence of insulin resistance. But does hyperinsulinemia precede and insulin resistance follow, or is it the reverse phenomenon which takes place? Insulin resistance has been clearly demonstrated in vitro (by analyzing the number of receptors, postreceptors and kinase activity) and in vivo (using clamp techniques), and it is just as evident in hepatocytes and myocytes. Overproduction of glucose by the liver usually has even more effect when it coexists with hyperinsulinemia. Insufficient binding of glucose to the muscles is partially related either to deficient glucose transport and/or to reduced activity of glycogen synthetase, explaining the deficiency of glycogen in the muscles, and of pyruvate dehydrogenase activity, decreasing the oxidation of glucose. Genetic studies have shown that insulin resistance is in many circumstances a genetically acquired defect. Does hyperinsulinemia, both absolute and relative, result from an anomaly in the insulin gene, insulin receptors, glucose transport, or in receptors for apolipoproteins and LDL? The exact mechanism has not yet been clarified, but each explanation remains plausible. Moreover, hyperinsulinemia is not the only secretory abnormality of NIDDM, and it appears that its association with erythrocyte sodium/lithium cotransport activity increases the risk of hypertension and nephropathy. The same is true of the increase in plasma endothelin and in the inhibitor of plasminogen activity. Levels of amylin, a peptide isolated from insular amyloid deposits, are increased in obese patients who are glucose intolerant or who have NIDDM, and levels show a good correlation with the degree of insulinemia. Amylin is not detectable in IDDM.
s2 While the pathophysiology thanks
to more suitable
of NIDDM
still remains
diets and ever increasing
poorly
defined,
improvements
most of the anomalies in insulin resistance, insulin secretion, ances. I would like to tell you about one such drug, gliclazide
its treatment
continues
to improve
in drugs which are capable
and associated or Diamicrons.
of correcting
endocrine-metabolic
disturb-
Gliclazide or Diamicrons normalizes the physiological insulin response after stimulation by glucose. It also restores the early peak of insulin secretion in the oral glucose tolerance test and increases total insulin secretion, while avoiding hyperinsulinism which might be harmful. Gliclazide controls blood glucose levels not simply by acting on insulin secretion but also by partly correcting insulin liver and even more so in the muscles where it stimulates glycogen synthetase. Gliclazide specific
actions
on small blood
vessels,
their endothelial
secretion
and on blood
resistance in the also has various
platelets.
In particular,
it corrects the decrease in plasma fibrinolytic activity, perhaps via the inhibitor of plasminogen. corrects excessive platelet aggregation and adhesiveness, and reduces the increased thrombotic of diabetics. This is the information that physicians need to have about NIDDM and gliclazide.
It also activity
It is not my role to introduce the twelve speakers who will take turns to tell us all the latest details concerning gliclazide: this will be done by the six moderators who. will come two by two to this platform throughout the afternoon. At this point in my introduction I would like you to remember this old Chinese proverb: ‘When you drink water, think of the source’. In fact, the source is Servier Laboratories with its President and Chief Executive Officer, Dr. Jacques Servier. In France we are very proud of this large pharmaceutical company which is considered one of the most important in our country. Its research laboratories keep it in the forefront of progress and it has recently been ranked first among world pharmaceutical companies for innovation. Gliclazide itself was developed at Servier Research Laboratories, fully justifying our meeting here today in Montreal. In expressing on your behalf all my thanks to the President and Chief Executive Officer of Servier Laboratories, I am also addressing who have played a very important role in ensuring that this antidiabetic could finally the Canadian market. I hope that Diamicronm will have a long and brilliant career.
myself to all those be introduced onto