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Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.

Rizza RA - Diabetes (2010)

Bottom Line: Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present.I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia.While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. rizza.robert@mayo.edu

ABSTRACT
The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present. The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

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A schematic portrayal of the splanchnic catheterization method. HA, hepatic artery; HV, hepatic vein; PV, hepatic vein (16).
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Figure 7: A schematic portrayal of the splanchnic catheterization method. HA, hepatic artery; HV, hepatic vein; PV, hepatic vein (16).

Mentions: Why was insulin-induced stimulation of glucose disappearance lower in the people with diabetes? Is insulin-induced stimulation of hepatic glucose uptake, muscle glucose uptake, or a combination of both decreased in people with type 2 diabetes? In order to address this question, Dr. Ananda Basu used the splanchnic catheterization method, whose development was pioneered by Dr. John Wahren (16). With this method, blood samples are simultaneously obtained from an artery and from the hepatic vein. Splanchnic blood flow is measured by infusing indocyanine green. Since both flow and glucose concentration are known, net splanchnic glucose balance (NSGB) (Fig. 7) can be calculated by subtracting the amount of glucose leaving the splanchnic bed from the amount of glucose entering. Splanchnic glucose uptake (SGU) also can be calculated if a glucose tracer is infused. For example, if 10 labeled molecules of glucose enter the splanchnic bed and 9 leave, then SGU must have been one. Since the ratio of labeled to unlabeled glucose in the artery is known, total SGU can be determined. Splanchnic glucose production (SGP) then is calculated as the algebraic sum of NSGB and SGU.


Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.

Rizza RA - Diabetes (2010)

A schematic portrayal of the splanchnic catheterization method. HA, hepatic artery; HV, hepatic vein; PV, hepatic vein (16).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963523&req=5

Figure 7: A schematic portrayal of the splanchnic catheterization method. HA, hepatic artery; HV, hepatic vein; PV, hepatic vein (16).
Mentions: Why was insulin-induced stimulation of glucose disappearance lower in the people with diabetes? Is insulin-induced stimulation of hepatic glucose uptake, muscle glucose uptake, or a combination of both decreased in people with type 2 diabetes? In order to address this question, Dr. Ananda Basu used the splanchnic catheterization method, whose development was pioneered by Dr. John Wahren (16). With this method, blood samples are simultaneously obtained from an artery and from the hepatic vein. Splanchnic blood flow is measured by infusing indocyanine green. Since both flow and glucose concentration are known, net splanchnic glucose balance (NSGB) (Fig. 7) can be calculated by subtracting the amount of glucose leaving the splanchnic bed from the amount of glucose entering. Splanchnic glucose uptake (SGU) also can be calculated if a glucose tracer is infused. For example, if 10 labeled molecules of glucose enter the splanchnic bed and 9 leave, then SGU must have been one. Since the ratio of labeled to unlabeled glucose in the artery is known, total SGU can be determined. Splanchnic glucose production (SGP) then is calculated as the algebraic sum of NSGB and SGU.

Bottom Line: Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present.I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia.While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. rizza.robert@mayo.edu

ABSTRACT
The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present. The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.

Show MeSH
Related in: MedlinePlus