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Life Extension Magazine June 2009

Nine Pillars of Weight Loss

Evaluation of glucose tolerance, post-prandial hyperglycemia and hyperinsulinemia influencing the incidence of coronary heart disease.

BACKGROUND: Recently, the frequency of patients who have glucose intolerance has been increasing in Japan. Glucose intolerance and insulin resistance/hyperinsulinemia are thought to influence the progression of atherosclerosis. The present study examined glucose tolerance, insulin resistance, post-prandial hyperglycemia/hyperinsulinemia and coronary risk factors by using 75 g oral glucose tolerance test (OGTT). PATIENTS AND METHODS: Coronary risk factors were examined and OGTT with measurement of plasma glucose and serum insulin was done to evaluate the glucose metabolism and insulin resistance in 263 patients who underwent coronary angiography; 202 subjects were diagnosed as having coronary heart disease (CHD) and 61 subjects were normal. We compared the two groups. RESULTS: The rate of having diabetes was significantly high in the CHD group. From the result of OGTT, 22.3% of CHD patients had diabetes mellitus and 36.6% had impaired glucose tolerance, thus the total glucose intolerance rate was 57.7% in the CHD group. No significant difference was noted in the homeostatic model assessment-R (HOMA-R), but glucose and insulin at 2 hours after OGTT were all significantly high in the CHD group. CONCLUSION: The rate of glucose intolerance and the levels of post-prandial glucose and insulin were high in the CHD group. We concluded that the post-prandial hyperglycemia and hyperinsulinemia influenced the incidence of CHD.

Intern Med. 2007;46(9):543-6

Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2%; 3.85 micromol Cr, 7.5 +/- 0.2%; 19.2 micromol Cr, 6.6 +/- 0.1%). Fasting glucose was lower in the 19.2-micromol group after 2 and 4 months (4-month values: placebo, 8.8 +/- 0.3 mmol/l; 19.2 micromol Cr, 7.1 +/- 0.2 mmol/l). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 micromol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 +/- 0.4 mmo/l; 19.2 micromol Cr, 10.5 +/- 0.2 mmol/l). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 micromol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Diabetes. 1997 Nov;46(11):1786-91

Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.

Hypertension. 2005 Aug;46(2):398-405

Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project.

OBJECTIVES: To test the hypothesis that the unusually low prevalences of insulin resistance (IR), metabolic syndrome (MS) and diabetes (DM) in Alaskan Eskimos, compared to American Indians, is related to the traditional Eskimo diet, high in C20-C22 omega-3 fatty acids (FAs). To determine if the relatively low blood pressures, low serum triglycerides and high HDL cholesterol levels in Eskimos result from high omega-3 FA consumption. STUDY DESIGN: Cross-sectional study. METHODS: We measured plasma FA concentrations in 447 Norton Sound Eskimos (35-74 years of age) and screened for DM, CHD and associated risk factors. A dietary assessment (24-hr recall) was obtained for comparison the day before the blood sampling. RESULTS: Plasma omega-3 FA concentrations were highly correlated with dietary omega-3 FAs and HDL levels and inversely correlated with plasma levels of insulin, 2-h insulin (OGTT), HOMI-IR, 2-h glucose (OGTT), triglyceride levels and diastolic blood pressure. CONCLUSIONS: High consumption of omega-3 FAs positively affects components of the MS, insulin sensitivity and glucose tolerance. This finding suggests that high consumption of C20-C22 omega-3 FAs protects against the development of the MS and glucose intolerance.

Int J Circumpolar Health. 2005 Sep;64(4):396-408

The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia.

AIM: Exaggerated postprandial lipemia is now accepted as an independent risk factor in atherogenesis in type 2 diabetes mellitus. We investigated if better glycemic control improves fasting and postprandial lipid profile in type 2 diabetic patients in the short-term. METHODS: Thirty-two type 2 diabetic patients were studied before and after desired glycemic regulation with gliclazide and metformin. Basal levels of glucose, total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, insulin, and C-peptide were evaluated at fasting state. Afterwards, patients were given a standard 400-kcal mixed meal as a breakfast, containing 35% fat. At the 2nd and the 4th hours after the breakfast, postprandial glucose, triglyceride, insulin, and C-peptide levels were determined again. RESULTS: Significant decrease was observed in total cholesterol levels after better glycemic regulation (p<0.05). Besides, triglyceride levels decreased significantly from 175.36+/-17.85 mg/dl to 138.73+/-14.93 mg/dl at fasting state (p<0.05), from 197.26+/-20.85 mg/dl to 154.15+/-14.61 mg/dl at the 2nd hour after mixed meal (p<0.05), and from 209.63+/-28.54 mg/dl to 155.63+/-15.68 mg/dl (p<0.05) at the 4th hour after the mixed meal, when better glycemic profile was provided. Area under curve for triglyceride levels decreased significantly with the better glycemic regulation (p<0.01). CONCLUSIONS: Improved glycemic regulation can lower the raised fasting and postprandial triglyceride levels which are important atherosclerotic risk factors in diabetic patients even in short-term. Since this improvement in triglyceride levels comes early, diabetic patients can be evaluated for fasting and postprandial triglyceride levels in the first month of therapy.

Exp Clin Endocrinol Diabetes. 2005 Feb;113(2):80-4

Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects.

OBJECTIVE: The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (S(i)) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS: Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction +12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and S(i) were assessed at baseline and month 6. RESULTS: At baseline, FCS was related to VAT and IHL (P < 0.05) but not to IMCL. FCS was also the strongest determinant of S(i) (P < 0.01). Weight loss at month 6 was 1 +/- 1% (control, mean +/- SE), 10 +/- 1% (CR), 10 +/- 1% (CREX), and 14 +/- 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P < 0.01), but IMCL was unchanged. S(i) was increased at month 6 (P = 0.05) in the CREX (37 +/- 18%) and LCD (70 +/- 34%) groups (P < 0.05) and tended to increase in the CR group (40 +/- 20%, P = 0.08). Together the improvements in S(i) were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS. CONCLUSIONS: Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

Diabetes Care. 2006 Jun;29(6):1337-44

Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss.

The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increasing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass procedures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and biliopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resistance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms.

Obes Surg. 2005 Apr;15(4):462-73

Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial.

CONTEXT: Dehydroepian-drosterone (DHEA) administration has been shown to reduce accumulation of abdominal visceral fat and protect against insulin resistance in laboratory animals, but it is not known whether DHEA decreases abdominal obesity in humans. DHEA is widely available as a dietary supplement without a prescription. OBJECTIVE: To determine whether DHEA replacement therapy decreases abdominal fat and improves insulin action in elderly persons. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from June 2001 to February 2004. PARTICIPANTS: Fifty-six elderly persons (28 women and 28 men aged 71 [range, 65-78] years) with age-related decrease in DHEA level. INTERVENTION: Participants were randomly assigned to receive 50 mg/d of DHEA or matching placebo for 6 months. MAIN OUTCOME MEASURES: The primary outcome measures were 6-month change in visceral and subcutaneous abdominal fat measured by magnetic resonance imaging and glucose and insulin responses to an oral glucose tolerance test (OGTT). RESULTS: Of the 56 men and women enrolled, 52 underwent follow-up evaluations. Compliance with the intervention was 97% in the DHEA group and 95% in the placebo group. Based on intention-to-treat analyses, DHEA therapy compared with placebo induced significant decreases in visceral fat area (-13 cm2 vs +3 cm2, respectively; P = .001) and subcutaneous fat (-13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 months of DHEA therapy compared with placebo (-1119 muU/mL per 2 hours vs +818 muU/mL per 2 hours, P = .007). Despite the lower insulin levels, the glucose AUC was unchanged, resulting in a significant increase in an insulin sensitivity index in response to DHEA compared with placebo (+1.4 vs -0.7, P = .005). CONCLUSION: DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.

JAMA. 2004 Nov 10;292(18):2243-8

Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year.

BACKGROUND: Visceral fat is a key regulator site for the process of inflammation, and atherosclerotic lesions are essentially an inflammatory response. METHODS AND RESULTS: Fifty-six healthy premenopausal obese women (age range 25 to 44 years, body mass index 37.2+/-2.2, waist to hip ratio range 0.78 to 0.92) and 40 age-matched normal weight women were studied. Compared with nonobese women, obese women had increased basal concentrations of tumor necrosis factor-alpha (TNF-alpha, P<0.01), interleukin-6 (IL-6, P<0.01), P-selectin (P<0.01), intercellular adhesion molecule-1 (ICAM-1, P<0.02), and vascular adhesion molecule-1 (VCAM-1, P<0.05). Vascular responses to L-arginine (3 g IV), the natural precursor of nitric oxide, were impaired in obese women: reductions in mean blood pressure (P<0.02), platelet aggregation to adenosine diphosphate (P<0.05), and blood viscosity (P<0.05) were significantly lower as compared with those in the nonobese group. Concentrations of TNF-alpha and IL-6 were related (P<0.01) to visceral obesity, as well as to adhesin levels and responses to L-arginine. After 1 year of a multidisciplinary program of weight reduction (diet, exercise, behavioral counseling), all obese women lost at least 10% of their original weight (9.8+/-1.5 kg, range 7.5 to 13 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (P<0.01) and adhesin (P<0.02) concentrations and with improvement of vascular responses to L-arginine. CONCLUSION: In obese women, endothelial activation correlates with visceral body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese women.

Circulation. 2002 Feb 19;105(7):804-9

Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages.

There is growing support for the protective role of soluble fibre in type II diabetes. Soluble fibre beta-glucan found in cereal products including oats and barley may be the active component. There is evidence of postprandial blunting of blood glucose and insulin responses to dietary carbohydrates when oat soluble fibre is supplemented into the diet but few trials have been carried out using natural barley or enriched barley beta-glucan products. The aim of this trial was to investigate the postprandial effect of a highly enriched barley beta -glucan product on blood glucose, insulin and lipids when given with a high-CHO food and a high-CHO drink. 18 lean, healthy men completed a 4 treatment intervention trial

comprising (i) high-CHO(food control), (ii) high-CHO(food+fibre), (iii) high-CHO(drink control), (iv) high-CHO(drink+fibre) where a 10g dose of barley beta-glucan fibre supplement (Cerogen) containing 6.31g beta-glucan was added to food and drink controls. There was an increase of glucose and insulin following all 4 treatments. Addition of the beta -glucan supplement significantly blunted the glycaemic and insulinaemic responses on the food (p<0.05) but not drink (p>0.05) treatments when compared to controls. The high-CHO breakfasts decreased total, LDL- and HDL-cholesterol from baseline to 60 mins postprandially but there were no differential effects of beta-glucan treatment on circulating lipids. We conclude that a high dose barley beta-glucan supplement can improve glucose control when added to a high-CHO starchy food, probably due to increased gastro-intestinal viscosity, but not when added to a high-CHO beverage where rapid absorption combined with decreased beta-glucan concentration and viscosity may obviate this mechanism.

Asia Pac J Clin Nutr. 2007;16(1):16-24

Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults.

CONTEXT: Dietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD). OBJECTIVE: To examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components. DESIGN AND SETTING: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. PARTICIPANTS: A total of 2,909 healthy black and white adults, 18 to 30 years of age at enrollment. MAIN OUTCOME MEASURES: Body weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values. RESULTS: After adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 microU/mL], P = .007; blacks: 92.4-82.6 pmol/L [13.3-11.9 microU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 microU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 microU/mL], P<.001). Fiber was also associated with blood pressure and levels of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fibrinogen; these associations were substantially attenuated by adjustment for fasting insulin level. In comparison with fiber, intake of fat, carbohydrate, and protein had inconsistent or weak associations with all CVD risk factors. CONCLUSIONS: Fiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.

JAMA. 1999 Oct 27;282(16):1539-46

Low body mass index in non-meat eaters: the possible roles of animal fat, dietary fibre and alcohol.

OBJECTIVE: To examine the associations of diet and other lifestyle factors with body mass index (BMI) using data from the Oxford Vegetarian Study. SUBJECTS: 1914 male and 3,378 female non-smokers aged 20-89 y at recruitment to the study. MEASUREMENTS: All subjects completed a diet/lifestyle questionnaire at recruitment giving details of their usual diet and other characteristics including height and weight, smoking and drinking habits, amount of exercise, occupation and reproductive history. Answers to the food frequency questionnaire were used to classify subjects as either meat eaters or non-meat eaters, and to estimate intakes of animal fat and dietary fibre. Subjects were further classified according to their alcohol consumption, exercise level, social class, past smoking habits and parity. RESULTS: Mean BMI was lower in non-meat eaters than in meat eaters in all age groups for both men and women. Overall age-adjusted mean BMIs in kg/m2 were 23.18 and 22.05 for male meat eaters and non-meat eaters respectively (P < 0.0001) and 22.32 and 21.32 for female meat eaters and non-meat eaters respectively (P < 0.0001). In addition to meat consumption, dietary fibre intake, animal fat intake, social class and past smoking were all independently associated with BMI in both men and women; alcohol consumption was independently associated with BMI in men, and parity was independently associated with BMI in women. After adjusting for these factors, the differences in mean BMI between meat eaters and non-meat eaters were reduced by 36% in men and 31% in women. CONCLUSIONS: Non-meat eaters are thinner than meat eaters. This may be partly due to a higher intake of dietary fibre, a lower intake of animal fat, and only in men a lower intake of alcohol.

Int J Obes Relat Metab Disord. 1998 May;22(5):454-60

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