Reports from the United States and United Kingdom highlight recent research in diabetes.

Study 1: Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women.

According to recent research published in the journal Diabetes Care, “Consumption of a meal high in resistant starch or soluble fiber (beta-glucan) decreases peak insulin and glucose concentrations and areas under the curve (AUCs). The objective was to determine whether the effects of soluble fiber and resistant starch on glycemic variables are additive.”

“Ten normal-weight (43.5 years of age, BMI 22.0 kg/m(2)) and 10 overweight women (43.3 years of age, BMI 30.4 kg/m(2)) consumed 10 tolerance meals in a Latin square design. Meals (1 g carbohydrate/kg body wt) were glucose a ne or muffins made with different levels of soluble fiber (0.26, 0.68, or 2.3 g beta-glucan/100 g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g muffin),” wrote K.M. Behall and colleagues, Beltsville Human Nutrition Research Center.

The results indicated, “Overweight subjects had plasma insulin concentrations higher than those of normal-weight subjects but maintained similar plasma glucose levels. Compared with low beta-glucan-low resistant starch muffins, glucose and insulin AUC decreased when beta-glucan (17 and 33%, respectively) or resistant starch (24 and 38%, respectively) content was increased.

“The greatest AUC reduction occurred after meals containing both high beta-glucanhigh resistant starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight women were somewhat more insulin resistant than control women.”

The authors concluded, “Soluble fiber appears to have a greater effect on postprandial insulin response while glucose reduction is greater after resistant starch from highamylose cornstarch. The reduction in glycemic response was enhanced by combining resistant starch and soluble fiber. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism in both normal and overweight women.”

Behall and colleagues published their study in Diabetes Care (Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women. Diabetes Care, 2006;29(5):976-981).

For additional information, contact K.M. Behall, USDA ARS, Beltsville Human Nutrition Research Center, BARC E, Diet & Human Performance Laboratory, Bldg 307B, Beltsville, MD 20705, USA.

Study 2: Exenatide treatments demonstrated reductions in postprandial plasma glucose excursions in type 2 diabetes.

“Exenatide is an incretin mimetic whose effect on glycemic control in patients with type 2 diabetes is currently under investigation. This study assessed the effect of injection time relative to a standardized meal on postprandial pharmacodynamics of exenatide in patients with type 2 diabetes,” researchers in England report.

H. Linnebjerg and colleagues at Eli Lilly explained, “Eighteen patients participated in this single-center, open-label, placebo-controlled, randomized, six-way crossover study.

Patients received subcutaneous injections of either placebo (-15 min) or 10 mcg of exenatide at - 60, -15, 0, +30 or +60 min relative to a standardized breakfast meal on six consecutive days.

Serial blood samples were assayed for plasma glucose and insulin concentrations.”

They data indicated, “For all exenatide treatments, incremental postprandial glucose area under the postprandial plasma glucose curve from zero to 6 h (AUC[0-6 h]) was significantly reduced compared with placebo. When exenatide was administered before (-60, -15 min) or with the meal (0 min), peak postprandial glucose concentrations were significantly decreased (p<0.0001 for all treatments) compared with placebo.

“Post-meal exenatide administration (+30, p<0.05; +60 min, p=0.21) resulted in smaller peak glucose reductions and in some patients transient low plasma glucose concentrations were reported. Peak plasma insulin concentrations in the pre-meal treatments were significantly lower than placebo (p <0.05 for all treatments), while post-meal dosing groups exhibited a trend towards higher insulin peaks compared with placebo. The most common adverse events related to exenatide were headache, nausea, dyspepsia and vomiting, and were generally of mild-to-moderate intensity.”

“In this study,” concluded the authors, “all exenatide treatments demonstrated reductions in postprandial plasma glucose excursions compared with placebo. Pre-meal and with meal administration of exenatide produced greater reduction of postprandial glucose excursions compared with post-meal administration. These data support flexible dosing of exenatide at any time within 60 min before a meal.”

Linnebjerg and colleagues published their study in Diabetic Medicine (Exenatide: effect of injection time on postprandial glucose in patients with Type 2 diabetes. Diabet Med, 2006;23(3):240-245).

For additional information, contact H. Linnebjerg, Eli Lilly, Lilly Research Center Ltd, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England.

Study 3: Shift to L phenotype in enteroendocrine cells is linked to new onset type 2 diabetes.

According to recent research from the United States, “Among the products of enteroendocrine cells are the incretins glucagon-like peptide-1 (GLP-1, secreted by L cells) and glucose-dependent insulinotropic peptide (GIP, secreted by K cells). These are key modulators of insulin secretion, glucose homeostasis, and gastric emptying. Because of the rapid early rise of GLP-1 in plasma after oral glucose, we wished to definitively establish the absence or presence of L cells, as well as the relative distribution of the incretin cell types in human duodenum.”

M.J. Theodorakis and colleagues at the National Institute on Aging reported, “We confirmed the presence of proglucagon and pro-GIP genes, their products, and glucosensory molecules by tissue immunohistochemistry and RT-PCR of laser-captured, single duodenal cells. We also assayed plasma glucose, incretin, and insulin levels in subjects with normal glucose tolerance and type 2 diabetes for 120 min after they ingested 75 g of glucose.”

They discovered, “Subjects with normal glucose tolerance (n=14) had as many L cells (15(plusminus)1), expressed per 1,000 gut epithelial cells, as K cells (13(plusminus)1), with some containing both hormones (L/K cells, 5(plusminus)1). In type 2 diabetes, the number of L and L/K cells was increased (26(plusminus)2; p<0.001 and 9(plusminus)1; p<0.001, respectively).

“Both L and K cells contained glucokinase and glucose transporter-1, -2, and -3.

Newly diagnosed type 2 diabetic subjects had increased plasma GLP-1 levels between 20 and 80 min, concurrently with rising plasma insulin levels. Significant coexpression of the main incretin peptides occurs in human duodenum. L and K cells are present in equal numbers.”

The researchers concluded, “New onset type 2 diabetes is associated with a shift to the L phenotype.”

Theodorakis and colleagues published their study in American Journal of Physiology - Endocrinology and Metabolism (Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab, 2006;290(3):E550- E559).

For additional information, contact M.J. Theodorakis, National Institute on Aging, Diabetes Sect, Laboratory Clinic Invest, NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA.