| Management |
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| Post-Prandial Hyperglycemia |
Ashok Kumar DasDirector, Professor & Head of Medicine, JIPMER
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| Inverted U-shaped curve |
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| In 1968, “Reaven and Miller” demonstrated, in patients later labeled under the category of impaired glucose tolerance, a greater response after a glucose challenge than either non-diabetic or frankly diabetic individuals – a phenomenon which they labeled the “inverted U-shaped curve”. This hyperinsulinmeia is now thought to reflect the presence of insulin resistance. |
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| In normal individuals there is an acute rise in insulin in response to an orally ingested glucose load. Porte and coworkers10 showed that there is a loss of this early or first-phase glucose induced insulin. |
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| Secretion indicating probable beta cell dysfunction. |
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| Incretin |
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| When glucose is ingested orally insulin secretion is potentiated by still undefined alimentary factors included under the term incretin. Incretins may either be neutral or gastro-intestinal hormones. Prominent candidates are gastric inhibitory polypeptide ‘GIP’ and glucagon-like peptide 1 (GLP-1). |
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| Ahren B et. al11 in a study conducted in Sweden involving post-menopausal women, found that basal levels of GIP and GLP-1 were similar in IGT and in those with normal glucose tolerance. However, in response to an oral glucose load the plasma increase in GIP was reduced in women with IGT whereas the GLP-1 response to oral glucose was not different between the two groups. Thus, GIP may be the incretin that is defective in IGT and type 2 diabetes mellitus. |
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| Insulin sensitivity, glucose effectiveness and beta-cell function |
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| Significant alterations have been found in the insulin sensitivity, glucose effectiveness and beta-cell function in patients with IGT. |
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| In a study on African – Americans. Oser K et al12 demonstrated that while resting serum insulin and C-peptide levels tended to be greater in the type 2 diabetic and the IGT groups, the post-prandial responses were blunted as compared to the effect in those with normal glucose tolerance. The insulin sensitivity index was significantly lower in the IGT and the type 2 diabetic groups. Glucose effectiveness was found to be similar in all the three groups. |
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| Insulin kinetics and muscle morphology |
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| Glucose intolerance is also related to the resistance of peripheral tissues to the actions of insulin. The muscle fiber composition has been shown to influence glucose intolerance. |
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| In a study conducted in Norway, Toft L et al13 discovered that patients with IGT had a higher percentage of insulin-insensitive type 2 muscle fibers which are not adapted for fat oxidation. IGT patients also had less NEFA (non-esterified fatty acids) suppression and elevated NEFA levels as compared to controls with matched BMI. |
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| Metabolic abnormalities |
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| In IGT many of the metabolic abnormalities of DM are already present & provide insight into the pathogenesis of post-prandial hyperglycemia14. Impaired early insulin release is the most consistent defect almost universally observed. Insulin resistance, attributable mainly to obesity, decreased physical fitness, or glucose toxicity is also often present. |
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| The main reason that post-prandial hyperglycemia occurs in IGT is impaired suppression of endogenous (hepatic & renal) glucose release; this can be largely explained by impaired early insulin & impaired suppression of glucagon release. Post-prandial glucose disposal is normal or increased, the result of hyperglycemia & delayed hyperinsulinemia. Postabsorptive (fasting) rates of glucose release & disposal & circulating levels of free fatty acids, glycerol, ketone bodies, lactate & alanine are generally normal. |
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| Though the hepatic glucose production is normal, there is an increase in the fasting plasma insulin, suggestive of hepatic insulin resistance. The insulin resistance can be easily demonstrated by the euglycemic clamp technique. |
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| There is reduced uptake by muscle tissues. The beta cell response to glucose is impaired, the incretin effect is reduced & in addition there may be disturbances in free fatty acid metabolism that may alter intracellular glucose metabolism. |
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| Tavndou A et al15 have found a univariate association between vitamin A levels & insulin resistance. In multivariate logistic regression analysis, the relative risk or subjects with high vitamin A concentrations having IGT was 38. |
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| Green GM et al16 studied gastric emptying in Zucker type 2 diabetic rats. They showed that faster gastric emptying in these rats as compared to normal rats led to PPHG cholecystokinin & secretion, which slowed gastric emptying, led to reduced post-prandial blood sugars. |
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| However, in a study by Frank JW et al17, gastric emptying in NIDDM & healthy volunteers was not significantly different. In these diabetics they found that increased glucagon production & reduced early phase insulin secretion led to increased hepatic glucose output & resulted in PPHG. |
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| Dinneen S et al18 studied the effect of glucose ingestion in IDDM patients & the role of glucagon. They showed that impaired suppression of glucagon secretion in IDDM patients led to increased hepatic glucose output & thus resulted in PPHG. |
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| Alzaid AA et al19 assessed the action of insulin & glucose effectiveness in diabetic & nondiabetic humans. They showed that, in NIDDM, there is profound extra-hepatic insulin resistance & modest hepatic insulin resistance while glucose effectiveness was the same in NIDDM & normal subjects. They postulated PPHG to be due to this insulin resistance. |
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| Clinical Implications & Rationale for Treatment |
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| It has been demonstrated that achieving round-the-clock blood glucose control will lead to normalization of the HbA1C in diabetic patients. A normal HbA1C has been associated with fewer complications, morbidity & mortality in diabetic patients. Thus there is a dire need to control the post-prandial sugars in blood glucose levels. Moreover, it is now recognized that post-prandial hyperglycemia is a strong risk factor for coronary heart diseases morbidity & mortality. |
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| Post-prandial hyperglycemia is often associated with post-prandial lipemia, further increasing the cardiovascular risk due to the enhanced lipid peroxidation studies20 also link PPHG with cognitive decline, especially in the elderly diabetics. |
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| When fasting sugar is controlled, HbA1C depends on PPHG. Avignon A et al21 studied individuals with type 2 diabetes & showed that post lunch plasma glucose levels were better predictors of glycemic control. There was a better correlation of PPHG with HbA1C than fasting glucose levels. |
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| Various epidemiological studies22,23 have correlated PPHG with the presence of diabetic complications notable retinopathy and nephropathy. The correlation of PPHG has been found to be similar to that of HBA1C. |
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