[b said: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.
[b said:Quote[/b] ]Title: The Determinants of Glycemic Response to Diet Restriction and Weight Loss in Obesity and NIDDM.
Authors: Markovic TP, Jenkins AB, Campbell LV, Furler SM, Kraegen EW, and Chisholm DJ.
Abstract:
Objectives: To examine the mechanisms by which weight loss improves glycemic control in overweight subjects with NIDDM, particularly the relationships between energy restriction, improvements in insulin sensitivity, and regional and overall adipose tissue loss.
Research Design and Methods: Hyperinsulinemic glucose clamps were performed in 20 subjects (BMI=32 kg/m2, age=48) with normal glucose tolerance (n=10) or mild NIDDM (n=10) before and on the 4th and 28th days of a reduced-energy (1,100 kcal) formula diet. Body composition changes were assessed by dual x-ray absorptionmetry and insulin secretory changes were measured by insulin response to intravenous glucose before and after weight loss.
Results: In both groups, energy restriction at the 4th day reduced fasting plasma glucose, which was independently related to reduced carbohydrate intake. There was a marked increase by the 4th day in percent insulin suppression of hepatic glucose output in both groups. By the 28th day with 6.3 kg weight loss, plasma glucose was further reduced in the NIDDM group only, and insulin sensitivity increased in both groups. Only loss of abdominal fat related to improvements of plasma glucose and insulin sensitivity after weight loss. In contrast to insulin action, there were only small changes in insulin secretion.
Conclusions: Both energy restriction and weight loss have beneficial effects on insulin action and glycemic control in obesity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects relate to changes in abdominal fat.
Dr. Sears Comments: This study appeared the same month that I presented our Type 2 data at the American Diabetes Association. The balance of macronutrients and amount of calorie restriction in this study was virtually identical to the Zone Diet. Not surprisingly, the clinical results were also virtually identical to our results. The most striking observation was that insulin resistance and fasting insulin levels were dramatically reduced within four days, and in the absence of any significant weight loss. This study also answers the chicken and the egg question: does weight gain cause increased insulin or does increased insulin levels precede weight gain? The answer is the latter since insulin levels and insulin resistance are lowered prior to any weight loss. This study demonstrates that others can replicate the effects of the Zone Diet, and that the hormonal changes are seen within days.
[b said:Quote[/b] ]The Journal of the American Dietetic Association 1998;98(9):s1,a43
(Dr. Sears' comments are at the end of the abstract.)
TITLE: A COMPREHENSIVE STUDY OF A 1500 CALORIE 40/30/30 DIET VS. 1500-CALORIE STEP 1 DIET ON BODY COMPOSITION AND BLOOD PARAMETERS IN OVERWEIGHT ADULTS.
AUTHORS: D. Kalman MS, RD, Peak Wellness. Greenwich, CT; C.M. Colker, M.D., Greenwich Hospital. Greenwich, CT; J. Roufs MS, RD, NVI. Phoenix, AZ; I. Wilets, Ph.D., Beth Israel Medical Center. New York, NY; J. Antonio, Ph.D., University of Texas. Arlington, TX.
LEARNING OUTCOME: To determine, what effects if any, macronutrient manipulation would have on body composition, energy levels and blood parameters.
ABSTRACT: Twenty-nine overweight men and women (body mass >25) participated in this six-week outpatient study. The participants were randomized to either a 1500 calorie 40/30/30 diet [40% CHO] (n=14) or a 1500 calorie Step 1 diet [60% CHO] (n=15). The 40/30/30 diet consisted of 40% CHO, 30% protein, 30% fat, the Step 1 diet consisted of 60% CHO, 15% protein, and 25% fat. All subjects participated in Universal Circuit Training ™, one hour, three times per week supervised by an exercise physiologist. All subjects met two to four times (avg.=3) over six weeks with a registered dietitian for review and analysis of compliance to the study diets. Both groups lost a significant amount of weight (p<0.05) after 6 weeks of treatment (40% CHO, -2.8kg; 60% CHO, -1.2kg). However, the 40% CHO group lost more weight and a greater amount of body fat (-2.6kg; p<0.05), while the 60% CHO (-1.0kg) group did not achieve significant fat loss. There were no significant changes for both groups in serum glucose, HgBA1C, total cholesterol, HDL, LDL, or triglycerides during the study. Profile of Mood States (POMS) for fatigue and vigor was also analyzed in both study groups with the following results: 44% reduction in fatigue (p<0.05) for the 40% CHO group with a corresponding 15.7% increase in vigor (non-significant; p>0.05). The changes within the 60% CHO group did not achieve significance in either fatigue or vigor. In conclusion, the 1500 calorie 40/30/30 diet resulted in a significantly greater fat and weight loss compared with the 1500 calorie Step 1 diet over 6 weeks.
Dr. Sears' comments: This abstract is a very compelling argument against the common nutritional mantra that "a calorie is a calorie." Both diets tested were isocaloric, differing only in the macronutrient composition. The protein-to-carbohydrate ratio in the Zone Diet was 0.75, whereas in the American Heart Association Diet the protein-to-carbohydrate ratio was 0.25. The fact that exercise was part of the study also eliminated that factor in analyzing the data on weight loss and reduction of body fat. The fat loss in the participants following the Zone Diet was 260 percent greater than those following the American Heart Association Step 1 diet. This difference is even more impressive since participants following the Zone Diet consumed 20 percent more fat than the participants on the Step 1 diet. Furthermore, the fat loss in the Zone Diet was statistically significant (meaning it was reproducible) whereas the in the Step 1 group it was not. In terms of subjective measurements of fatigue reduction and increased vigor, the Zone Diet was again superior to the Step 1 diet. The lack of effect of the Zone Diet on triglyceride levels was probably due to inadequate levels of Omega-3 fatty acids in the diet. Unfortunately, fasting insulin levels were not analyzed in this study (as with other Zone studies) to correlate insulin reduction with loss of body fat. Other than those two items, this study is a very important step forward in the validation of the Zone Diet by other researchers.
[b said:Quote[/b] ]Clin Invest Med 1999 Aug;22(4): 140-148
(Dr. Sears' comments are at the end of the abstract.)
Title: Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects.
Authors: Wolfe BM; Piche LA.
Abstract:
Objective: To determine the effect on plasma lipid profiles of replacement of dietary carbohydrate by low-fat, high-protein foods.
Design: Cross-over randomized controlled trial
Participants: Ten healthy, normolipidemic subjects (8 women and 2 men).
Interventions: Subjects were randomly allocated to either a low-protein (12%) or high-protein (22%) weight-maintaining diet for 4 weeks and then switched to the alternate diet for 4 more weeks. The first 2 weeks of each diet served as an adjustment/washout period. Fat was maintained at 35% of energy, mean cholesterol intake at 230 mg per day and mean fibre intake at 24 g per day. Compliance was promoted by the use of written dietary protocols based on the food preferences of the subjects and weekly dietary consultation as required.
Results: Consumption of the high- versus low-protein diet resulted in significant reductions in mean plasma levels of total cholesterol (3.8 v. 4.1 mmol/L, p < 0.05), VLDL cholesterol (0.20 v. 0.26 mmol/L, p < 0.02), LDL cholesterol (2.4 v. 2.6 mmol/L, p < 0.05), total triglycerides (0.69 v. 0.95 mmol/L, p < 0.005) and VLDL triglycerides (0.35 v. 0.57 mmol/L, p < 0.001), as well as in the ratio of total cholesterol to HDL cholesterol (3.1 v. 3.5, p <0.01). A trend towards an increase in HDL cholesterol (1.26 v. 1.21 mmol/L, p = 0.30) was observed but was not statistically significant. Satiety levels tended to be higher among those eating the high-protein diet (6.1 v. 5.4, p = 0.073).
Conclusions: Moderate replacement of dietary carbohydrate with low-fat, high-protein foods in a diet containing a conventional level of fat significantly improved plasma lipoprotein cardiovascular risk profiles in healthy normolipidemic subjects.
Dr. Sears Comments: This is another crossover study comparing the Zone Diet to a high-carbohydrate diet while containing equal amounts of calories and fat using healthy volunteers with normal lipid levels. The Zone Diet (with a protein-to-carbohydrate ratio of .5) showed statistically significant improvements in lipid parameters after only four weeks. Compared to the high-carbohydrate diet (with a protein-to-carbohydrate ratio of 0.3), the individuals following the Zone Diet had a 7% decrease in total cholesterol, an 8% decrease in LDL cholesterol, and a 27% decrease in triglycerides along with a 4% increase in HDL cholesterol. These same improvements in lipid levels for the Zone Diet have already been reported for hypercholesterolemic and postmenopausal women and male elite distance runners. It appears that everyone would benefit from following the Zone Diet.
[b said:Quote[/b] ]Am J Clin Nutr 70: 221-227 (1999)
(Dr. Sears' comments are at the end of the abstract.)
Title: Dietary Protein and the Risk of Ischemic Heart Disease in Women.
Authors: Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Speizer FE, Hennekens CH, and Willett WC.
Abstract:
Background: Ingestion of animal protein raises serum cholesterol in some experimental models but not in others, and ecologic studies have suggested a positive association between animal protein intake and risk of ischemic heart disease. Prospective data on the relation of protein intake to risk of ischemic heart disease is sparse.
Objective: The objective was to examine the relation between protein intake and risk of ischemic heart disease.
Design: The study was a prospective cohort study.
Results: We examined the association between dietary protein intake and incidence of ischemic heart disease in a cohort of 80,082 women aged 34-57 y and without a previous diagnosis of ischemic heart disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Intakes of protein and other nutrients were assessed with validated dietary questionnaires. We documented 939 major instances of ischemic heart disease during the 14 y of follow-up. After age, smoking, total energy intake, percentages of energy from specific types of fat, and other ischemic heart disease risk factors were controlled for, high protein intakes were associated with a low risk of ischemic heart disease: when extreme quintiles of total protein intake were compared, the relative risk was 0.74. Both animal and vegetable proteins contributed to the lower risk. The inverse association was similar in women with low-or high-fat diets.
Conclusions: Our data does not support the hypothesis that a high protein intake increases the risk of ischemic heart disease. In contrast, our findings suggest that replacing carbohydrates with protein may be associated with a lower risk of ischemic heart disease. Because a high dietary protein intake is often accompanied by increases in saturated fat and cholesterol intakes, application of these findings to public dietary advice should be cautious.
Dr. Sears Comments: The women with the lowest incidence of heart disease followed a Zone Diet with a protein-to-carbohydrate ratio of 0.7 (near the center of the Zone). They also consumed less bread, less starch, and consumed more protein, fruits and vegetables than the other women. These modifications (which are exactly those recommended on the Zone Diet) resulted in a 24% reduction in heart disease.
This study represents a long-term consequence of following the Zone Diet is the reduction of heart disease. This is the reason I developed the Zone Diet many years ago.
Insulin maes you fat just like carrots are high GI[b said:Quote[/b] (Keebler Elf @ Feb. 06 2003,1:52)]But insulin makes you fat
