Postprandial Blood Glucose Excursions Research Articles

Drug therapy of postprandial hyperglycaemia.

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.

Insulin lispro, a new insulin analog.

Insulin lispro is a rapid-acting insulin analog to regular insulin. Inversion of the proline-lysine amino acid sequence at positions 28 and 29 on the B chain is responsible for its more rapid absorption, faster onset, and shorter duration of action compared with regular insulin. The fast onset of action allows for greater flexibility in dosing and mealtime scheduling. Insulin lispro provides equivalent or slightly improved glycemic control in patients with types I and II diabetes mellitus compared with regular insulin, without subsequent increases in hypoglycemic episodes. It also results in greater reduction in postprandial blood glucose excursion than regular insulin. Compared with other insulins, insulin lispro represents a more physiologic approach to exogenous insulin therapy.

Optimal Time of Administration of Insulin Lispro. Importance of meal composition

To compare the glucodynamics of pre- and postprandial administration of insulin lispro using test meals of differing composition. Twenty subjects with IDDM were studied on four separate occasions. Ten subjects ingested high-carbohydrate and high-fat breakfasts with a large liquid component, and 10 subjects ingested high-carbohydrate and high-fat breakfasts in a more solid form. With each meal, insulin lispro was injected 10 min preprandial on one occasion and 20 min postprandial on another. The magnitude and temporal pattern of postprandial glucose excursions were observed. With all meal types studied, postprandial blood glucose excursions were significantly smaller when insulin lispro was administered preprandially (P < 0.05). With both high-carbohydrate meals and the liquid high-fat meal, preprandial administration of lispro was associated with modest postprandial increments of blood glucose. With the solid high-fat meal, preprandial lispro produced a cumulative decline in postprandial blood glucose, whereas blood glucose rose when lispro was administered postprandially. For meals with a high carbohydrate content, the optimal time of administration of lispro is preprandial. However, for meals with a high solid fat content, postprandial administration of lispro may be preferable.

Does Suppression of Postprandial Blood Glucose Excursions by the α-Glucosidase Inhibitor Miglitol Improve Insulin Sensitivity in Diet-Treated Type II Diabetic Patients?

Insulin sensitivity is impaired in patients with type II diabetes and is exacerbated by high mean blood glucose (BG). Potentially, large postprandial swings in BG could result in further decrements of insulin sensitivity. Because alpha-glucosidase inhibitors cause a marked reduction in the amplitude of BG changes, the aim of this study was to determine if such a BG-smoothing effect improves insulin sensitivity in well-controlled type II diabetic subjects treated with diet alone. Patients received either miglitol (BAY m 1099) (50 mg three times daily) or placebo for 8 weeks in a randomized double-blind parallel study. The miglitol (9 men, 2 women) and placebo (7 men, 3 women) groups were well matched (mean +/- SD) for age, weight, and blood glucose control (fasting BG, 6.4 +/- 1.0 vs. 6.9 +/- 1.6 mmol/l; HbA1, 7.7 +/- 1.0 vs. 7.9 +/- 0.4%; fructosamine, 0.99 +/- 0.08 vs. 1.07 +/- 0.17 mmol/l). The glucose metabolic clearance rate was calculated during the last 30 min of a 150 min glucose/insulin sensitivity test (glucose, 6 mg . kg-1 . min-1; insulin, 0.5 U . kg-1 . min-1). There was no significant improvement in metabolic clearance rate (0.21 +/- 0.27 vs. 0.16 +/- 0.35 l . kg-1 . min-1) for the miglitol- and placebo-treated groups, respectively. There were no statistically significant differences between miglitol and placebo for changes from baseline in BG (0.1 +/- 0.1 vs. -0.1 +/- 0.2 mmol/l), HbA1 (0.1 +/- 0.1 vs. 0.3 +/- 0.1%), and fructosamine (-0.06 +/- 0.02 vs. -0.03 +/- 0.02 mmol/l). Alpha-glucosidase-induced improvement in postprandial hyperglycemia does not result in increased insulin sensitivity.

Pharmacology of α‐glucosidase inhibition

AbstractThe development of α‐amylase and brush‐border α‐glucosidase inhibitors is reviewed. The mode of action as well as pharmacological and pharmacodynamic properties of selected inhibitors with special regard to the most thoroughly investigated α‐glucosidase inhibitor acarbose are discussed. Inhibition of intestinal α‐glucosidases delays the digestion of starch and sucrose, flattens the postprandial blood glucose excursions, and thus mimics the effects of dieting on hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. Therefore, the mechanism of α‐glucosidase inhibition represents the pharmacological optimization of the dietary principle of delayed carbohydrate absorption.In pre‐clinical studies using diabetic animals the oral administration of acarbose improved the metabolic state and reduced the blood glucose area under the curve. As a consequence, the process of non‐enzymatic glycation of proteins was retarded as indicated by reduced glycated haemoglobin, glomerular basement membranes or advanced glycation end‐products (AGEs) in collagen. These improved biochemical parameters correlated with beneficial effects against the development of diabetic nephropathy and neuropathy. Thus, the treatment of diabetic animals with acarbose does not only improve the metabolic state but has also the potential to delay, or possibly prevent, the development of diabetic complications.

Acarbose and insulin therapy in type I diabetes mellitus.

In this paper relevant studies are summarized regarding the use of acarbose as an adjunct to insulin in the treatment of type I diabetes. It is concluded that this approach may contribute to a reduction of postprandial blood glucose excursions and a smoothening of daily blood glucose profiles, an improvement of metabolic control as expressed by glycosylate haemoglobin values and a reduction of insulin requirements. Long-term studies are, however, necessary before one can conclude that addition of acarbose to the therapeutic regimen in type I diabetic subjects is of longstanding value.

Management dilemmas in the individual with cystic fibrosis and diabetes

As their life expectancy has improved, patients with cystic fibrosis (CF) have experienced an increasing incidence of diabetes. Hyperglycemia may adversely influence weight, pulmonary function, and development of microvascular complications. Strict control of blood glucose has not universally been sought, however. A program of multiple daily insulin injections and self-monitoring of blood blucose with an aim of normoglycemia is described in this article. The typical cystic fibrosis diet is variable in quantity and features a preponderance of simple carbohydrates; this is contrary to the usual diabetes meal plan. We describe the use of a flexible meal-planning system to establish individualized carbohydrate targets with specific insulin boluses titrated to each meal to control postprandial blood glucose excursions. Records of 22 patients followed for more than 1 year are reviewed. Mean (±standard error of the mean) glycosylated hemoglobin was reduced from 11.3±3.1% (at baseline) to 8.1±1.8% (at 1 year). Mean percent of ideal body weight also increased from 95.4±15.2 to 100±17.1. We conclude that strict metabolic control is an attainable goal in patients with cystic fibrosis and is associated with positive weight gain.