OBJECTIVE--To determine whether a chronic low--glycemia index (LGI) diet, compared with a high glycemia index (HGI) diet, has beneficial effects on plasma glucose control, lipid metabolism, total [at mass, and insulin resistance in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS--Twelve type 2 diabetic men were randomly allocated to two periods of 4 weeks of an LGI of HGI carbohydrate diet separated by a 4-week washout interval, in a crossover design
RESULTS--The LGI diet induced lower postprandial plasma glucose and insulin profiles and areas under the curve than after the HGI diet. At the end of the two dietary periods, the 7 day dietary records demonstrated equal daily total energy and macronutrient intake Body weight and total tat mass were comparable. Four week LGI versus HGI diet induced improvement of lasting plasma glucose (P < 001, [DELTA] changes during LGI vs. HGD, Hb[A.sub.1c], (P < 0.01), and whole body glucose utilization measured by the euglycemia-hyperinsulinemic clamp (P < 0.05) LGI diet induced a decrease in fasting plasma total and LDL cholesterol ([DELTA] changes LGI vs HGI, P < 0.01), free fatty acids (P < 0.01). apolipoprotein B, and plasminogen activator inhibitor 1 activity.
CONCLUSIONS--Only 4 weeks of an LGI diet was able to improve glycemia control, glucose utilization, some lipid profiles, and the capacity for librinolysis in type 2 diabetes. Even if changes in glycemia control were modest during the 4-week period, the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders.
**********
Diabetes is a chronic evolving disease associated with a variety of micro-and macrovascular complications, increasing postprandial plasma glucose and insulin excursions are assumed (1,2) to increase severity of diabetes and to be independent predictors of risk for atherosclerotic diseases. As such, interventions to reduce postprandial plasma glucose and insulin peaks are one of the essential therapeutIc objectives for diabetic patients and could reduce the risk of developing cardiovascular complications.
Because dietary carbohydrate is one of the main factors in controlling postprandial hyperglycemia, it is reasonable to question whether the type of dietary carbohydrate can modify the evolution and complications of this disease in a clinically significant long-term fashion.
There is growing recognition that the postprandial glycemia (3,4) and insulinemic (5) responses to different foods may vary despite equal amounts of total absorbable carbohydrates. This concept favors the use of low-glycemia index (LGI) carbohydrates. Although focusing on the total amount of carbohydrate intake is important for diabetic patients (6,7), using LGI carbohydrates could lead to additional benefits without increasing the fat content of the diet and consequently increasing plasma free fatty acids (FFAs), with all their deleterious consequences (8).
Whether the glycemia index (GI) of foods has relevance to human health has been a topic of contention. In the literature, there is evidence from some intervention studies that consuming LGI foods is associated with improvement of several measures of carbohydrate metabolism and cardiovascular risk factors in type 2 diabetes (9-12). Even if some studies (13) could not demonstrate a statistically significant improvement in plasma glucose control, the decline in Hb[A.sub.1c] levels was twice as great on the LGI dietas on the high-glycemia index (HGI) diet. Until now, however, some professional organizations have taken the position that there is no evidence that chronic consumption of LGI foods will contribute to improved glycemia in people with diabetes (6,7). They have mentioned that in type 2 diabetes, the number of studies comparing LGI with HGI diets for 2 weeks or longer is limited.
Moreover, in a previous study in nondiabetic slightly overweight subjects, such a diet resulted in decreased total fat mass as well as the expression of some genes implicated in lipid metabolism (14).
Thus, the aim of the present study was to evaluate whether the chronic use of an LGI diet compared with an HGI diet might modify plasma lipids, plasma glucose responses and control, insulin sensitivity, and fat distribution in a homogeneous group of type 2 diabetic men. Furthermore, we aimed to determine the effect of these diets on fibrinolysis as a marker of cardiovascular risk.
RESEARCH DESIGN AND METHODS--Twelve type 2 diabetic men volunteered to participate in this study. The clinical and biological characteristics of these subjects are given in Table 1. Subjects with abnormal renal, hepatic, and thyroid functions were excluded. One patient was under a dietary regimen alone and 11 patients were receiving antidiabetic agents. None of the patients were or had been treated with insulin. All therapies were continued unchanged throughout the study. The Ethical Committee of Hotel-Dieu Hospital approved the experimental protocol. The purpose, nature, and potential risks of the study were explained, and a written informed consent was obtained from each subject.
Study design
The patients were randomly allocated to two periods of 4 weeks of an LGI or HGI diet in a crossover design. The two nutritional periods were separated by a washout interval of 4 weeks. Before the beginning of the study, all the subjects were instructed to maintain their usual lifestyle during the experimental period.
At the beginning and the end of each nutritional period, subjects were hospitalized for 2 days after an overnight fast. During the first day, an indwelling cannula was inserted into an antecubital vein. This cannula served for the hourly withdrawal of blood samples during the 8-h metabolic profile. Each subject consumed an LGI or HGI breakfast at 0830 and lunch at 1230. The meals during the 1-day profile were the same as during the chronic period with HGI of LGI. Blood samples were collected in the fasting state (time 0) and hourly during the 8-h metabolic profile. Blood samples were centrifuged, and plasma was frozen (-20[degrees]C) for further measurements of plasma glucose, insulin, and lipids (triacylglycerols, cholesterol, and FFAs). At time 0, plasma apolipoprotein Band plasminogen activator inhibitor (PAI)-1 levels were also measured. During the first day, body lean and fat mass distributions were also measured by dual-energy X-ray absorptiometry (DEXA) with a total-body DEXA scanner (Holojic QDR-2000), as described previously (15).
During the second day, three blood samples were taken at the fasting state, with 5-min intervals, to measure the homeostasis model assessment (HOMA).
The estimation of pancreatic [beta]-cell function and insulin sensitivity was calculated using the HOMA/CIGMA software (16).
Glucose turnover and hepatic glucose production
The studies of glucose dynamics were part of the studies done on the second-day hospitalization and consisted of a first step of 180 min of [6,6-[sup.2][H.sub.2]]glucose (Mass Trace, Wohurn, MA) infusion followed by one step of insulin infusion: a high dose of insulin of 6 mU x [kg.sup.-1] x [min.sup.-1] (180 min).
In the morning of the experiment, at 0800, one catheter was placed in an antecubital vein for infusion of [6, [6,6-[sup.2][H.sub.2]]glucose. Another catheter was placed retrogradely into a contralateral wrist vein for blood sampling. Venous blood was arterialized by placing the hand in a heated box (70[degrees]C). A priming dose of [6,6-[sup.2][H.sub.2]] glucose was determined according to basal individual plasma glucose concentrations. After the priming dose, the infusion rate was maintained at 3 mg x [kg.sup.-1] x [h.sup.-1] during 3 h. Blood samples were withdrawn before the isotope infusion and at 10-min intervals during the last 30 min to determine the [6,6-[sup.2][H.sub.2]] glucose enrichment.
The calculation of the hepatic glucose production was made according to the formula [R.sub.a] = i/Ep, where [R.sub.a] is the rate of glucose appearance, i is the tracer infusion rate, and Ep is the [6,6-[sup.2][H.sub.2]] glucose isotopic enrichment in the plasma, based on the assumption that the plasma glucose steady state was achieved (17). In the basal state, the turnover of glucose equals the hepatic glucose production.
Euglycemia-hyperinsulinemic clamp studies
A one-step clamp study was then performed at an insulin infusion of 6 mU x [kg.sup.-1] x [min.sup.-1] (180 min) as described previously (18). During the infusion of this high insulin dose of 6 mU x [kg.sup.-1] x [min.sup.-1] hepatic glucose production was supposed to be zero (19), so that the exogenous glucose infusion provides a measurement of the total-body glucose disposal.
Dietary follow-up
