Postprandial Hyperglycemia In Patients Research Articles

Effect of acarbose on postprandial lipid metabolism in type 2 diabetes mellitus

The effect of acarbose, an α-glucosidase inhibitor, on postprandial glucose and lipid metabolism was investigated in patients with type 2 diabetes mellitus. Twenty patients (10 men and 10 women) with type 2 diabetes mellitus were studied. A test meal was taken with or without 100 mg of acarbose. The levels of plasma glucose, and serum immunoreactive insulin, lipids, apolipoproteins, and remnant-like particle cholesterol were investigated. Acarbose inhibited the postprandial increase of both plasma glucose and serum immunoreactive insulin. Acarbose also significantly suppressed the increase of serum triglycerides at 60, 90, and 120 min ( P<0.05 to P<0.01), and the increase of serum remnant-like particle cholesterol at 60 and 120 min ( P<0.05). Acarbose inhibited the postprandial decline of apolipoprotein C-II, and decreased the postprandial serum apolipoprotein C-III level. These results suggest that acarbose may improve postprandial hyperlipidemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166).

1. (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166), a novel oral hypoglycaemic agent is a non-sulphonylurea insulin secretagogue. 2. We investigated the insulin-releasing action and hypoglycaemic effect of A-4166 compared to sulphonylureas in vitro and in vivo. 3. A-4166 stimulated insulin secretion from rat freshly isolated pancreatic islets at concentrations from 3 x 10(-6) M to 3 x 10(-4) M in the presence of 2.8 mM glucose. There was no obvious difference in glucose dependency between the insulinotropic effect of A-4166 and that of glibenclamide, and no additive or synergistic effect was observed between these two drugs. 4. A-4166 displaced [3H]-glibenclamide bound to intact HIT-T15 cells in a concentration-dependent manner. The Ki value was 4.34 +/- 0.04 x 10(7) M, and the displacement potency of A-4166 was between that of glibenclamide and tolbutamide, being similar to that of gliclazide. 5. Inf fasted beagle dogs, A-4166 showed a dose-dependent hypoglycaemic effect after oral administration over the range 1 to 10 mg kg-1. The hypoglycaemic action of A-4166 showed an earlier onset and a shorter duration than that of sulphonylureas. 6. Simultaneous measurement of plasma insulin levels revealed that the hypoglycaemic effect of A-4166 was caused by a rapid-onset and brief burst of insulin secretion. 7. The pharmacokinetic profile of A-4166 was consistent with the changes of the blood glucose and plasma insulin levels. 8. Although the in vitro insulin-releasing effect of A-4166 was similar to that of sulphonylureas, its hypoglycaemic effect was more rapid and shorter-lasting, associated with rapid absorption and clearance. Thus, A-4166 may be useful in suppressing postprandial hyperglycaemia in patients with non-insulin-dependent diabetes mellitus.

Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus

Background & Aims : The roles of hyperglycemia in diabetic gastroparesis and gastric delivery in postprandial hyperglycemia of diabetic patients are unclear. The aims of this study were to assess gastric emptying and its relation to postprandial glucose metabolism in patients with asymptomatic non-insulin-dependent diabetes mellitus (NIDDM) and no autonomic neuropathy and to identify motor mechanisms responsible for any accelerated gastric emptying. Methods : Autonomic function, gastric emptying, postprandial glucose metabolism, and hormone levels (glucagon, insulin, cholecystokinin, glucose-dependent insulinotropic polypeptide, neurotensin, and peptide YY) were assessed in healthy volunteers and patients with NIDDM. In a second study, gastric tone and motility were measured in patients with accelerated gastric emptying and in controls. Results : Gastric emptying of solids did not differ in the two groups, but liquids emptied faster in patients with NIDDM ( P < 0.02). The rate of entry of ingested glucose into the systemic circulation was similar, but higher postprandial glucagon and lower insulin concentrations led to greater ( P < 0.01) postprandial hepatic glucose release. Levels of other enteropeptides, gastric accommodation, and antral motility were similar, but patients with NIDDM had greater proximal gastric phasic contractions than controls ( P < 0.05). Conclusions : Excessive hepatic glucose release, not rapid entry of ingested glucose, is the primary cause of postprandial hyperglycemia in patients with NIDDM. Accelerated gastric emptying in patients with nonneuropathic NIDDM is associated with increased proximal stomach phasic contractions.

Could intranasal insulin be useful in the treatment of non-insulin-dependent diabetes mellitus?

To evaluate whether intranasal insulin might be useful as a meal-adjunct in the treatment of NIDDM we compared plasma glucose and insulin responses to a mixed breakfast (9 kcal/kg, 50% carbohydrate) following either intranasal insulin (INI) or placebo in eleven patients with NIDDM. Five patients treated with subcutaneous insulin and in good to moderate glycemic control and six patients who were ‘failing’ on oral agents and in poor glycemic control were studied. In the patients usually on sc insulin, INI inhibited postprandial hyperglycemia. Lower doses (1 U/kg vs 1.5 U/kg b.w.) were needed to accomplish this in 2 patients with low fasting glucose (≤7.8 mmol/l) than in three patients with higher fasting glucose (10.5 ± 0.5 mmol/l). In the patients on oral agents who had marked fasting hyperglycemia (14.8 ± 0.8 mmol/l) an only transient reduction (for 90 to 120 min) of postprandial hyperglycemia was achieved when INI (1 U/kg) was given in addition to po glyburide (10 mg) prior to the meal. Following placebo in the group previously treated with sc insulin, plasma free insulin levels increased maximally by 23 mU/l, 75 min after the meal. The group on oral agents had a comparable but later peak increment (at 180 min) indicative of an even greater impairment of endogenous insulin secretion in response to hyperglycemia. Following INI, the peak increment in plasma insulin occurred earlier (30 min after the meal) and was greater in all patients (55 ± 18, 139 ± 68, 86 ± 24 mU/l respectively for the prior sc insulin therapy group at doses of 1.0 and 1.5 U/kg and for the oral agent group at 1.0 U/kg). In summary, intranasal insulin can reduce postprandial hyperglycemia in patients with NIDDM by increasing early postprandial insulin levels. It is more effective in those with less severe fasting hyperglycemia. Since elevated insulin levels and glucose lowering effect are transient, nasal insulin would need to be added to a regimen achieving fasting glucose control through diet, oral agents or long-acting subcutaneous insulin.

Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2-3H] or [3-3H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus as has been proposed for fasting hyperglycemia, excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM.

α-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus

In patients with diabetes mellitus, delayed increases in circulating insulin levels followed by prolonged hyperinsulinemia due to slow absorption of subcutaneously administered insulin hinders maintenance of euglycemia. To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an α-glucosidase inhibitor (Acarbose ® Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion. When 25% less insulin (9 v 12 units) was given along with Acarbose 30 minutes prior to meal ingestion, postprandial hyperglycemia decreased by 45% (areas under the curve, AUC, 8193 ± 1960 v 14783 ± 2260 mg/dL · min, P < 0.02). When similar amounts of insulin (12 units) were given immediately prior to mean ingestion, postprandial hyperglycemia decreased 55% (AUC 6187 ± 2240 v 13642 ± 1579 mg/dL · min, P < 0.001). These results indicate that delay in carbohydrate absorption improves the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and may permit satisfactory postprandial glycemic control when insulin is administered immediately prior to meal ingestion. Thus, an agent like Acarbose, which delays carbohydrate absorption, may be useful as an adjunct to insulin in the treatment of diabetes mellitus.

Effect of source of dietary carbohydrate on plasma glucose, insulin, and gastric inhibitory polypeptide responses to test meals in subjects with noninsulin-dependent diabetes mellitus

Previous reports have documented the fact that plasma glucose and insulin responses can vary in response to the ingestion of different carbohydrate-rich foods. This has led to the creation of a “glycemic index,” a classification of dietary carbohydrates on the basis of the relative rise in plasma glucose after the administration of the food in question as compared to a standard glucose challenge. In order to test the clinical utility of these observations, we evaluated plasma glucose, insulin, and gastric inhibitory polypeptide responses to four major sources of carbohydrate (potato, rice, spaghetti, lentil) as part of a conventional mixed meal in patients with noninsulin-dependent diabetes mellitus. Each test meal provided 40% of the subjects' calculated caloric requirement and contained 15% of total calories as protein, 40% as fat, and 45% as carbohydrate. The test carbohydrate represented 66% of total carbohydrate. The results indicated that plasma glucose concentrations after meals containing equal amounts of carbohydrate as rice, spaghetti, or lentil were similar and somewhat lower than meals containing potato. The plasma insulin responses to the four carbohydrate foods paralleled the glucose responses. Changes in gastric inhibitory polypeptide levels did not account for the effect of potato. These results are totally disparate from what would have been predicted by previously published values for the “glycemic index” of the four foods studied, and suggest that a “glycemic index” based on isolated challenges would have minimal clinical utility in efforts aimed at reducing postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus.