Introduction

Obesity is central in the pathogenesis of type 2 diabetes and plays a major role in the inferior metabolic control in these patients. Type 2 diabetes is also associated with dyslipidemia, characterized by increased plasma triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and an increased number of small, dense low-density lipoprotein (LDL) particles.¹ This atherogenic lipoprotein profile probably contributes to the very high cardiovascular risk and mortality of type 2 diabetic patients.² Several studies have shown that weight loss obtained through very low calorie diet (VLCD) can improve glycemic control in overweight type 2 diabetics.^3,4,5,6,7 The efficacy of a less restricted low calorie diet (LCD) to correct the atherogenic lipid profile in these patients has not yet been evaluated. In the present study, NMR spectroscopy was used to determine compositional changes in lipoproteins in type 2 diabetic patients after 8 weeks full diet-replacement with a commercial LCD (850 kcal/day).

Materials and methods

In all, 11 overweight type 2 diabetics (three males/eight females), four of these treated with oral hypoglycemic agents (OHA), were enrolled in the study. Subject characteristics at baseline are as follows: means.e.m age 625.7 y (57–73); duration of diabetes 3.7 y (1.5–8); diabetes treatment 4 OHA/7 diet; body mass index (BMI) 36.85.5 kg/m² (30.4–46.8); waist/hip ratio 0.93 (0.83–1.09); hemoglobin A_1c (HbA_1c) (%) 7.00.7; fasting blood glucose 7.92.1 mmol/l; systolic blood pressure 15514 mmHg; diastolic blood pressure 817 mmHg; values are given as means.d.

Medication was discontinued in all four subjects taking OHA for 2 weeks prior to the intervention and throughout the whole 8-week intervention period. Subjects visited the clinic nine times during the 8-week intervention period for weight and blood glucose control. They received an 850 kcal/day diet in the form of a powdered preparation, which was reconstituted to a liquid formula (Nutrilett^® NutriPharma, Oslo, Norway) containing 97 g protein, 81 g carbohydrate, and 15 g fat. The diet supplied all nutrients according to RDA. The diet was divided into eight portions, each containing 107 kcal, to be spread over the day. Three different flavors were available: strawberry, chocolate, and bouillon. Lipid profile was assessed by NMR analysis at the beginning and end of the intervention. Metabolic parameters were measured fasting at baseline and after completion of the 8-week LCD (Table 1).

Table 1 - Clinical characteristics, plasma parameters, and lipid profile of the subjects (n=10) at baseline and after 8-week LCD.

Full table

Blood samples were taken at the beginning and end of the 8-week intervention period. Intake of alcohol and participation in sports were not allowed on the day before blood sampling. For NMR LipoProfile analysis, venous blood samples were collected into 3 ml tubes containing 0.1% EDTA after an overnight fast (>10 h) and centrifuged immediately at 3000 r.p.m. for 10–15 min. A measure of 1 ml of EDTA plasma was transferred to Nunc Cryotubes and frozen at -80°C. All samples from this study were shipped together on dry ice to LipoMed in Raleigh, NC for analysis.

For HbA_1c analysis, venous blood samples were collected into 3 ml EDTA tubes after an overnight fast (>10 h) and frozen immediately at -20°C. Lipoprotein subclass profiles were measured by proton NMR spectroscopy as described previously.⁸ HbA_1c was analyzed by a turbidometric immunassay.⁹

Statistical analysis was performed with SPSS software. Data were tested for Gaussian distribution with Shapiro–Wilks normal distribution test prior to analysis. t-Tests were used for comparison of all Gaussian distributed parameters. Non-Gaussian data paired comparisons were analyzed with Wilcoxon's signed-rank test. Differences were considered to be significant at P<0.05. Results are expressed as meanss.e.m.

Results

In all, 10 patients completed the 8-week treatment with LCD. One patient was excluded from the data analysis due to refusal to use the LCD as the sole source of nutrition.

Clinical characteristics and plasma biomarkers of the 10 completers at baseline and following 8 weeks of LCD treatment are shown in Table 1. Weight, waist circumference, insulin, HbA1c, and fasting blood glucose (FBG) all fell significantly following the LCD. The mean weight loss was 10.9 kg, 11% of initial body. Two of the four patients who were taking OHA on inclusion did not have to restart OHA therapy at the end of the study.

The observed weight reduction was associated with favorable changes in plasma cholesterol, LDL cholesterol, and fasting triglyceride. Total cholesterol fell by 20% (P<0.001), LDL cholesterol by 17% (P<0.05), and fasting triglyceride by 39% (P<0.05). There were large, insignificant, positive changes in the LDL subclass distribution. Large LDL particles (LDL 1) increased by 75% (P=0.169), medium (LDL 2) decreased by 31% (P=0.170), and small (LDL 3) decreased by 82% (P=0.221). LDL size increased insignificantly from 20.6 to 21.1 nm (P=0.108). There was a shift in the distribution of HDL subclasses. Small HDL particles (HDL 3) decreased significantly by 21% (P=0.008), and medium HDL particles (HDL 2) increased by 36% (not significant) (P=0.147) (Table 1).

Discussion

The major weight loss obtained, with marked improvements in glycemic control and risk factors, was very similar to results seen in type 2 diabetics on much more restrictive VLCDs (<400 kcal/day).^3,4,5,6,7 Studies in simple obese subjects have shown that diets providing 400, 600, and 800 kcal/day produce similiar weight losses,¹⁰ but the safety of diets providing less than 800 kcal/day is questionable. In the present study, LCD induced weight loss, with associated improvements in glycemic control, comparable to that produced by VLCD, and that weight reduction after LCD has a beneficial effect on lipid profile. Cross-sectional studies have shown that the cardio-protective effect of HDL cholesterol is most strongly associated with the larger HDL 2 particles in both non-diabetics^11,12 and in type 2 diabetic patients,¹³ but a weaker positive association between HDL 3 cholesterol and CHD has also been described.¹⁴ Shifts in LDL and HDL subfractions toward larger and less dense particles lowers the risk of cardiovascular disease.^15,16,17 That the changes observed in subclass distribution did not reach statistical significance was probably due to the high methodological coefficient of variation.

Conclusions

The present results suggest that short-term use of LCD is very effective in improving glycemic control and in partially correcting dyslipidemia by promoting weight loss in overweight type 2 diabetic patients.

Declaration of interests

The study was supported by a grant from Nutri-Pharma Ltd, London, UK. None of the authors have any financial interests in the company. A Astrup is a member of the external scientific council of Nutri-Pharma Ltd, UK.

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