Quote[/b] ]A Nutrition Intervention Program to Improve Glycemia, Lipid Profiles, and Hyperinsulinemia in Patients with Type 2 Diabetes
BARRY SEARS, PAUL KAHL, GEORGE RAPIER, Marblehead, MA and San Antonio, Tx, USA.
Introduction
It is believed that Type 2 diabetes can be primarily controlled by diet. However, diets routinely prescribed to these patients have less than expected clinical benefits despite intensive education programs and materials.
We designed a clinical trial using similar calorie ranges used by the American Diabetes Association but with a macronutrient ratio consisting of 40% carbohydrate, 30% protein and 30% fat to determine whether clinically significant improvement in blood parameters can be achieved in free-living Type 2 diabetics.
Methods
Subjects
Seventy patients with Type 2 diabetes greater than one-year duration were recruited from Princeton Medical Management Resources (PMMR) in San Antonio, TX. During the previous year, all had undergone intensive individual nutrition counseling according to American Diabetes Association guidelines. Each subject signed a consent form provided by PMMR.
Trial Design
The diet consisted of three meals and two snacks daily. The amount of dietary protein was individualized to maintain the subject's lean body mass (LBM). The average protein amount for males was approximately 100 grams/day and for females, 75 grams/day. The minimal protein for any subject was 75 grams/day, divided between 3 meals and 2 snacks.
The protein-to-carbohydrate ratio for each meal and snack was approximately 0.75. The fat content for each meal/snack was adjusted to provide 30% of the total calories. Any added fat was primarily monounsaturated. The five meals per day consisted of breakfast, lunch, late afternoon snack, dinner and a late evening snack. Each snack was approximately 100 calories. The total caloric intake varied from 1,100 (minimal allowed) to 2,000 calories daily depending on individual protein requirements.
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Nutrition bars consisting of 20 grams carbohydrate, 14 grams protein, and 7 grams fat equaling 190 calories provided breakfast and the two snacks. The snacks used one-half bar. The bars provided 40 mg. eicosapentaenoic acid (EPA) and 0.5 mg gamma linolenic acid (GLA) and were fortified with 19 vitamins and minerals. The RDA for these vitamins and minerals was met or exceeded by the ingestion of two bars/day.
Additionally, molecularly distilled fish oil containing 1080 mg of EPA were supplied in six soft gelatin capsules to be taken with meals. Eicotech Corporation, Marblehead, MA, supplied both the nutrition bars and capsules.
All subjects were required to attend four one-hour weekly group sessions. During this period, they received information on food composition, meal preparation, and food shopping according to the above dietary guidelines. Dietary meal plans for each subject based on their protein requirements and meal preferences were provided.
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Results
The results after six weeks in subjects with Type 2 diabetes are shown in Table 1.
Table 1.
Six Week Results with Type 2 Diabetics (n=68)
Parameter 0 Wks 6 Wks % Diff p value
Insulin 28 21 -23 p<0.0001
FBS 167 153 -8 p=0.03
HbA1c 7.8 7.3 -7 p<0.0001
Tot. Chol 203 202 0 n.s.
LDL Chol 123 122 0 n.s.
HDL Chol 45 49 8 p<0.0001
TG 189 162 -14 p=0.002
TC/HDL 4.7 4.3 -9 p<0.0001
TG/HDL 4.2 3.1 -26 p<0.0001
Weight 188 188 0 n.s.
Fat Mass 72 70 -3 p<0.0001
Even though there was no loss in body weight (although there was a decrease in fat mass), statistically significant improvements were observed in glycemic control, lipid profiles and fasting insulin ratios. Additional blood chemistry was done at 12 weeks. The results are shown in Table 2.
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Table 2
12-Week Results with Type 2 Diabetics (n=56)
Parameter 0 Wks 12 Wks % Diff p value
HbA1c 7.7 7.3 -6 p<0.0001
FBS 164.4 158 -5 n.s.
Total Chol 200 200 0 n.s
LDL Chol 121.8 123.7 +2 n.s.
HDL Chol 45.8 50.2 +9 p<0.0001
TG 170 130 -20 p<0.0004
TC/HDL 4.4 4 -9 p<0.0001
TG/HDL 3.7 2.7 -27 p<0.0001
Weight 191 184 -4 p<0.0001
Only 1 out of 34 patients in this second group using insulin at the start of the study required insulin at the twelve week time point. Unlike the six week point, there was now statistically significant weight loss at the twelve week period. All other lipid parameters were basically unchanged from the six-week mark.
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Discussion
The benefits of any dietary intervention require long-term compliance. Although this was a calorie restricted diet, compliance was good during the 12-week period (79% completed the clinical trial). Part of this compliance may have been that they were responsible for only two meals per day. Fewer than 10% of the subjects complained of hunger.
As seen from the 12-week data points, the benefits achieved at six weeks were maintained. Although there was a slight increase in patient's fasting blood sugar, we believe this reflects the large reduction in glycemic lowering medication during the course of the trial. Of 34 patients using exogenous insulin at the start of the study, only one patient continued insulin injections by week 12.
Lipid profiles, in particular triglycerides and HDL cholesterol, improved significantly. Recent studies have indicated that an elevated triglyceride to HDL cholesterol ratio is strongly associated with both an increase in the amounts of atherogenic small, dense LDL particles and increased myocardial infarction risk (Gaziano et al. Circulation 96: 2520-2525, 1997). Reduction of the triglyceride/HDL cholesterol ratio illustrates significant improvement in this cardiovascular risk parameter with this nutritional intervention used in this study.
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We believe that many of the clinical improvements ultimately may be explained by the reduction of insulin levels on eicosanoid formation. Hyperinsulinemia is known to activate the delta-5-desaturase enzyme that increases the formation of arachidonic acid (AA) from dihomo gamma linolenic acid (DGLA) [Pelikanova et al. Clinica Chimica Acta 203: 329-338, 1993]. Thus, lowering insulin levels should reduce AA production with a corresponding increase in DGLA.
Supplementation with combinations of EPA and GLA can promote further improvement in the DGLA/AA ratio. EPA acts as a feedback inhibitor of delta-5-desaturase, while supplementation with GLA ensures an adequate substrate for the formation of DGLA. Changing the ratio of DGLA to AA in target tissues, especially in the vascular bed, increases the likelihood of generating eicosanoids that are vasodilatory, anti-inflammatory and anti-thrombotic. Simultaneously, there will be less production of eicosanoids that are vasoconstrictive, pro-inflammatory and pro-thrombotic. This change in eicosanoid balance would have a significant effect on endothelial cell function.
Endothelial cell dysfunction is known to be present in Type 2 diabetics (Pinkney et al. Diabetes 46: S9-S13, 1997). We believe endothelial cell dysfunction may be an underlying cause of insulin resistance by limiting insulin access to its target tissues. A favorable eicosanoid balance may enhance endothelial cell function providing insulin access to the target cell receptors. Better glucose homeostasis would be achieved with lower insulin levels under this hypothesis. Our results are consistent with recently published studies using calorie restricted formula diets consisting of 38% carbohydrates, 33% protein, and 29% fat (Markovic et al. Diabetes Care 21: 695-700, 1998) which demonstrated reduced insulin levels and improved insulin sensitivity within four days after institution of a similar dietary program.
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Conclusions
A protein-adequate, carbohydrate-moderate, low-fat, calorie-restricted diet can be integrated readily into the lifestyle of patients with Type 2 diabetes, providing highly significant clinical improvements within six weeks in hyperinsulinemia, glycemia, and lipid profiles as shown below:.
Insulin 23% decrease
HbA1c 7% decrease
TG 14% decrease
TG/HDL 26% decrease
The decrease in each of the risk factors indicates the Zone Nutritional Program has significant potential in reducing the cardiovascular risk that is elevated in Type 2 diabetics.
Dr. Sears' comments: This study was the first to demonstrate that the Zone Diet can lower insulin levels, decrease the ratio of triglycerides to HDL cholesterol, and reduce glycosylated hemoglobin levels in short period of time in Type 2 diabetics.
The changes in these clinical parameters are not only important in the treatment of Type 2 diabetics, but also are paramount for reversing the aging process.
