| Management |
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| Post-Prandial Hyperglycemia |
Ashok Kumar DasDirector, Professor & Head of Medicine, JIPMER
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| De Vecian et al24 compared preprandial blood sugar & post prandial blood sugar with respect to the outcome of pregnancy. They that normalizing post-prandial blood sugars was associated with better outcomes of pregnancy. |
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| The primary importance of PPHG lies in its association with coronary heart disease (CHD). The Honolulu heart Study25 evaluated the role of PHG in the risk of fatal CHD. There was a significant increase in the risk of CHD as the 1-hour post 50 gm glucose load serum glucose levels increased. |
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| In the Whitehall study (1980)26, mortality doubled in patients with post-prandial blood sugar values between 96-196 mg/dl as compared to those with post-prandial blood sugar < 96 mg/dl. |
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| In the IsIigton Diabetes survey (1992 )27 the prevalence of major CHD increased from 9% in patients with normal glucose tolerance to 15% in patients with IGT. In the Diabetes Intervention Study (1997)28, a study of individuals with newly diagnosed type 2 DM seen in 16 diabetic clinics was conducted. The researchers found that PPHG, but not fasting hyperglycemia as an independent risk factor for myocardial infarction & total mortality. |
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| It is now very evident that CHD risk correlates with PPHG. However, it is not clear weather it is a direct relation to the hyperglycemia or whether it is secondary to other associated risk factors like hyperglycemia or it is secondary to other associated risk factors like hyperinsulinemia and clustering of metabolic cardiovascular risk factors. |
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| Hyperinsulinemia was detected to be a better predictor of morbidity & mortality than glucose values in the Paris Prospective Study29. |
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| DCCT4 & UKPDS30 results show that intensive therapy to maintain near-normal blood glucose levels help to prevent complications of DM. However, there is still no direct proof that targeting PPHG per se will lead to improvement in cardiovascular morbidity. |
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| Russel JC et al31 showed that in an atherosclerosis pone animal model acarbose treatment was associated with reduced lesions. |
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| The association of PPHG with post-prandial lipemia remains speculative at present. There is a correlation between post-prandial triglyceride levels & carotid artery sclerosis. It has been shown recently that post-prandial triglcyeride level as a predictor of CHD32. Studies are needed to document whether treatment of PPHG will reduce post-meal oxidative load. |
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| Treatment |
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| Non Pharmacological |
Pharmacological |
Diet Modifications
Diet Supplements
Use of supplement like sugar gum |
Insulin lispro
Amylin analogues
Alpha glucose inhibitors
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| Insulin kinetics and muscle morphology |
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| Non-Pharmacological Interventions |
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| Diet Modifications:The measures advocated include - |
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- Multiple small proportions of meals
- Substitution of carbohydrate with monounsaturated fatty acids.
- Modest restriction of carbohydrate
- Use of poorly digestible carbohydrate instead of refined, easily digestive ones
- Individualization of diet based on assessment of glycemic, index of foods
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| Diet Supplementation |
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| Soluble fibers like guar & oat gums. Some hemicelluloses have been tried. But these usually have found to have only a modest effect. |
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| Brenelli et al33 showed that guar gum, but not pectin was able to reduce PPHG by 35%. These effects were related to the viscosity characteristics of the gum. |
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| Pharmacological Therapy |
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| Short acting Insulin analogue ( Insulin Lispro, Insulin Aspart ) |
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| The Short acting Insulin analogue, Insulin Lispro, Insulin Aspart are novel genetically engineered insulins designed to act more rapidly & with a shorter duration than human regular insulin3. Proline & Lysine at positions B8 & B29 of human insulin were inverted in insulin lispro. In insulin aspart a single proline amino acid at position28 of insulin B chain has been replaced with aspartic acid. While the original indication for the short acting insulin analogs were to use as rapid acting pre-meal insulins, the recent expansion of clinical experience has revealed the benefits of short acting analogs means to reduce severe hypoglycemia, improve post-prandial glucose levels, improve glucose control as assessed by the HbA1C & enhance patient convenience & quality of life. |
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| Amylin |
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| Amylin is a pancreatic beta-cell hormone that is cosecreted with insulin. This was discovered in 1987. The mechanism of action include regulation of gastric emptying, suppression of postprandial glucagon secretion & replenishment of hepatic glycogen stores. However, the short half-life & tendency to aggregate limit the usefulness of this product. |
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| Amylin Analogues |
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| Pramlinitide |
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| This is an amylin with the difference being that amino acid residues at 25,28,29 have been replaced with proline. This prevents self-aggregation without diminishing its biological activity. This drug has to be administered as SC or IV injections. |
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| Kolterman OG et al39, studied patients with intravenous infusion of amylin analogue. They showed that the two-hour post prandial glucose excursions were lesser than controls. This goal was achieved by a slowing of gastric emptying time. |
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| Rosenstock 40 in a phase III trial treated 477 patients with type 1 DM with pramlintide or placebo. He found a significant net decrease in HbA1C in patients treated with pramlintide 30-60 mg, 4 times daily as compared to placebo. There was no increased frequency of hypoglycemia or increased weight gain. However large-scale trails are required. Also many patients with DM may already have delayed gastric emptying as a result of autonomic neuropathy. In addition glucagon secretion in many diabetics declines over time & cease to play a role in the development to hyperglycemia. The role of amylin analogues in these patients may be limited. |
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| Alpha-glucosidase inhibitors |
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| This group includes acarbose, miglitol & voglibose. Acarbose is the most widely studied. The main mechanism of action is through inhibition of carbohydrate digestion. It has been found that there is a 90% inhibition of glucoamylase, 65% inhibition of sucrase & 60% inhibition of maltase. |
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| Acarbose reduce post-prandial glucose level by 50mg/dl. There are no net nutritional losses. Studies have shown reduction in HbA1C by 0.5 – 1%, Acarbose can be used as monotherapy or a combination with sulphonylureas, metformin, or insulin. The adverse effects include flatulence, & loose stools. Tolerance to these effects occurs over 3 months. It is advisable to start at low doses & titrate slowly upwards to reduce the incidence of gastro-intestinal side effects. |
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| Meglitinide Analogues |
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| Repaglinide is an oral antidiabetic agent a new chemical entity belonging to the Meglitinide family. It is an insulin secretagogue, which has a specific receptor binding site. It has a rapid onset & a short duration action, that is particularly useful as a postprandial glucose regulator. Studies from Landgraft et al, ( vs glibenclamide ) , Owens ( vs glipizide ) & Gomis R ( vs glipizide ) have shown a superior efficacy of Repaglinide. Repaglinide is excreted predominantly through bile & is therefore relatively safe in the elderly & in patients with mild to moderate renal disease. It has a low risk of hypoglycaemia even after skipping a meal. Studies have proven its efficacy & safety in a wide range of patients. |
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