Ann M Coulston

Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia

We examined the relation between insulin resistance, plasma glucose and insulin responses to meals, lipoprotein lipase (LPL) activity, and postprandial lipemia in a population of 37 healthy nondiabetic individuals. Plasma glucose and insulin concentrations were determined at frequent intervals from 8 AM through midnight (breakfast at 8 AM and lunch at noon); resistance to insulin-mediated glucose disposal was determined by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of glucose, insulin, and somatostatin; LPL activity was quantified in postheparin plasma; and postprandial concentrations of triglyceride (TG)-rich lipoproteins were assessed by measuring the TG and retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20 to 400 lipoprotein fractions. Significant simple correlation coefficients were found between various estimates of postprandial lipemia and SSPG (r = .38 to .68), daylong insulin response (r = .37 to .58), daylong glucose response (r = .10 to .39), and LPL activity (r = -.08 to -.58). However, when multiple regression analysis was performed, only SSPG remained independently associated with both postprandial TG and retinyl palmitate concentrations. These data provide evidence that insulin resistance plays an important role in regulating the postprandial concentration of TG-rich lipoproteins, including those of intestinal origin.

Nutrition principles for the management of diabetes and related complications

Health professionals and people with diabetes recognize nutrition therapy as one of the most challenging aspects of diabetes care and education (1). Adherence to meal planning principles requires the person with diabetes to learn specific nutrition recommendations. It may require altering previous patterns of eating and implementing new eating behaviors, which requires motivation for a healthy lifestyle and may also require participation in exercise programs. Finally, individuals must be able to evaluate the effectiveness of these lifestyle changes. Despite these challenges, nutrition is an essential component of successful diabetes management.

Deleterious metabolic effects of high-carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus

The effects of variations in dietary carbohydrate and fat intake on various aspects of carbohydrate and lipid metabolism were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM). Two test diets were utilized, and they were consumed in random order over two 15-day periods. One diet was low in fat and high in carbohydrate, and corresponded closely to recent recommendations made by the American Diabetes Association (ADA), containing (as percent of total calories) 20 percent protein, 20 percent fat, and 60 percent carbohydrate, with 10 percent of total calories as sucrose. The other diet contained 20 percent protein, 40 percent fat, and 40 percent carbohydrate, with sucrose accounting for 3 percent of total calories. Although plasma fasting glucose and insulin concentrations were similar with both diets, incremental glucose and insulin responses from 8 a.m. to 4 p.m. were higher (p less than 0.01), and mean (+/- SEM) 24-hour urine glucose excretion was significantly greater (55 +/- 16 versus 26 +/- 4 g/24 hours p less than 0.02) in response to the low-fat, high-carbohydrate diet. In addition, fasting and postprandial triglyceride levels were increased (p less than 0.001 and p less than 0.05, respectively) and high-density lipoprotein (HDL) cholesterol concentrations were reduced (p less than 0.02) when patients with NIDDM ate the low-fat, high-carbohydrate diet. Finally, since low-density lipoprotein (LDL) concentrations did not change with diet, the HDL/LDL cholesterol ratio fell in response to the low-fat, high-carbohydrate diet. These results document that low-fat, high-carbohydrate diets, containing moderate amounts of sucrose, similar in composition to the recommendations of the ADA, have deleterious metabolic effects when consumed by patients with NIDDM for 15 days. Until it can be shown that these untoward effects are evanescent, and that long-term ingestion of similar diets will result in beneficial metabolic changes, it seems prudent to avoid the use of low-fat, high-carbohydrate diets containing moderate amounts of sucrose in patients with NIDDM.

Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans☆

Two levels of dietary carbohydrate (40% and 60% of calories) were incorporated into typical U.S. diets and fed for 10 days each to 11 healthy volunteers. Fasting blood samples were drawn on days 8, 9, and 10 of each dietary period and analyzed for glucose, insulin, cholesterol, triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations. In addition, plasma glucose, insulin and TG concentrations were determined before, and for 3 hr after the noon meal on days 8 and 10. No differences were observed in fasting plasma glucose, insulin or cholesterol concentrations. However, fasting plasma TG levels were significantly elevated on the 60% carbohydrate diet, and HDL-cholesterol concentrations were significantly decreased. Furthermore, the plasma insulin and triglyceride responses to the meal tolerance test during the 60% carbohydrate dietary period were significantly elevated. These results indicate that high-carbohydrate diets lead to changes in insulin, TG, and HDL-cholesterol concentrations which have been associated with an increase in incidence of coronary artery disease.

Why Do Low-Fat High-Carbohydrate Diets Accentuate Postprandial Lipemia in Patients With NIDDM?

OBJECTIVE To understand why low-fat high-carbohydrate (CHO) diets lead to higher fasting and postprandial concentrations of triglyceride (TG)-rich lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Patients with NIDDM were placed randomly on diets containing either 55% CHO, 30% fat, and 15% protein or 40% CHO, 45% fat, and 15% protein for 6 weeks, followed by crossover to the other diet. Test meals at the end of each diet period were consumed at 8:00 A.M. and 12:00 P.M. (noon) and contained 20 and 40% of daily calories, respectively. Vitamin A was also given at noon, and TG-rich lipoproteins of intestinal origin were identified by the presence of vitamin A esters. Frequent measurements were made throughout the 24-h study period of plasma glucose, insulin, and TG concentrations. Plasma samples obtained from 12:00 P.M. (noon) until 12 A.M. (midnight) were subjected to ultracentrifugation, and measurements were made of TG and vitamin A ester concentrations in plasma and in both the Svedberg flotation constant (Sf) >400 (chylomicron) and Sf 20-400 (chylomicron remnant) lipoprotein fractions. In addition, very-low-density lipoprotein (VLDL)-TG turnover rate was estimated by following the decay of [3H]VLDL-TG. Finally, postheparin lipoprotein lipase and hepatic lipase activities were measured at the end of each dietary period. RESULTS Mean ± SE hourly concentrations of glucose (8.0 ± 0.8 vs. 7.5 ± 0.7 mmol/1), insulin (184 ± 26 vs. 158 ± 19 pmol/1), and TG (2.8 ± 0.2 vs. 2.1 ± 0.2 mmol/1) were higher (P < 0.05-0.001) after the 55% CHO diet. The 55% CHO diet also led to an increase (P < 0.05-0.01) in the mean ± SE hourly concentrations of vitamin A esters in plasma (2.3 ± 0.3 vs. 1.6 ±0.1 μmol/l) and in both the chylomicron (2.0 ± 0.3 vs. 1.4 ±0.1 μmol/l) and chylomicron remnant fractions (0.36 ± 0.04 vs. 0.14 ± 0.03 μmol;/l). In addition, the VLDL-TG production rate was higher (17.2 ± 1.4 vs. 12.8 ± 1.0 mg · kg−1 · h−1, P < 0.003) and the VLDL-TG fractional catabolic rate lower (0.22 ± 0.02 to 0.28 ± 0.02 l/h, P < 0.005) after the 55% CHO diet. Finally, there was an increase in lipoprotein lipase activity (7.0 ± 0.8 to 8.1 ± 0.7 μmol free fatty acids released · ml−1 · h−1, P < 0.02) in response to the CHO-enriched diet. CONCLUSIONS A low-fat high-CHO diet in patients with NIDDM led to 1) higher day-long plasma glucose, insulin, and TG concentrations; 2) postprandial accumulation of TG-rich lipoproteins of intestinal origin; 3) increased production of VLDL-TG; and 4) increased postheparin lipoprotein lipase activity. These data provide a mechanism for the hypertriglycer-idemic effect of CHO-enriched diets in patients with NIDDM and demonstrate that multiple risk factors for coronary heart disease are accentuated when these individuals consume diets recommended to reduce this risk.

Persistence of hypertriglyceridemic effect of low-fat high-carbohydrate diets in NIDDM patients.

Although low-fat high-carbohydrate diets are recommended for patients with non-insulin-dependent diabetes mellitus (NIDDM) in an effort to reduce the risk of coronary artery disease (CAD), the results of short-term studies have shown that these diets can lead to changes in carbohydrate and lipid metabolism associated with an increased risk of CAD. This study has extended these earlier observations by determining the metabolic effects of such diets over a longer period in these patients. The comparison diets contained either 40 or 60% of the total calories as carbohydrates, with reciprocal changes in fat content from 40 to 20% consumed in random order for 6 wk in a crossover experimental design. The ratio of polyunsaturated to saturated fat and the total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P < .001) elevated throughout the day when patients consumed the 60% carbohydrate diet, and 24-h urinary glucose excretion more than doubled (0.8 vs. 1.8 mol/24 h). Fasting plasma total and very-low-density lipoprotein (VLDL) triglyceride (TG) concentrations increased by 30% (P < .001) after 1 wk on the 60% carbohydrate diet, and the magnitude of carbohydrate-induced hypertriglyceridemia persisted unchanged throughout the 6-wk study period. Total plasma cholesterol concentrations were similar after both diets. However, VLDL cholesterol (VLDL-chol) was significantly increased, whereas both low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol concentrations were significantly decreasedafter consumption of the 60% carbohydrate diet. Consequently, neither total-chol-to-HDL-chol nor LDL-chol-to-HDL-chol ratios changed. The results of this study indicate that high-carbohydrate diets lead to several changes in carbohydrate and lipid metabolism in patients with NIDDM that could lead to an increased risk of CAD, and these effects persist for >6 wk. Given these results, it seems reasonable to suggest that the routine recommendation of low-fat high-carbohydrate diets for patients with NIDDM be reconsidered.

Effect of Source of Dietary Carbohydrate on Plasma Glucose and Insulin Responses to Mixed Meals in Subjects With NIDDM

It has been demonstrated that carbohydrate-rich foods result in different plasma glucose responses when eaten alone by normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). This study was designed to test if the glycemic response to mixed meals can be altered by selecting carbohydrate-rich foods based on their glycemic potency. Consequently, three test meals were developed that should have yielded high-, intermediate-, and low-glycemic responses based on the published glycemic index of all the carbohydrate foods in the meals. The test meals were consumed by normal individuals and patients with NIDDM, and the resultant plasma glucose and insulin responses were determined. The results indicated that the plasma glucose responses after the meals did not vary as a function of their glycemic potency in either the normal or NIDDM subjects. There were no significant differences in the plasma insulin responses for either group. These results indicate that the plasma glucose response to mixed meals did not vary as a function of the calculated glycemic potencies. Therefore, the glycemic response to a mixed meal was not predicted on the basis of the published values of the glycemic index of the individual carbohydrate foods included in the meal.

The Effect of a Plant-Based Diet on Plasma Lipids in Hypercholesterolemic Adults: A Randomized Trial

Context People can achieve recommended fat intake while consuming high or low amounts of vegetables, fruits, legumes, and whole grains. Contribution This 4-week randomized trial compared 2 diets with different vegetable, fruit, legume, and whole-grain content but identical total fat, saturated fat, protein, carbohydrate, and cholesterol content. The 59 adults who consumed high amounts of vegetables, fruits, legumes, and whole grains had greater improvements in total and low-density lipoprotein cholesterol levels than the 61 adults who ate low amounts of these foods. Implications At least over the short term, greater improvements in low-density lipoprotein and total cholesterol are an additional benefit of diets high in vegetables, fruits, legumes, and whole grains. The Editors It is well established that elevated low-density lipoprotein (LDL) cholesterol concentrations are a risk factor for cardiovascular diseases and that dietary modification is considered a first approach to their treatment and control (1, 2). For several decades, dietary modification for lipid management traditionally focused on avoiding saturated fat and cholesterol (3-5). Previous examples of dietary interventions targeting LDL cholesterol level often reported only modest lipid improvements, leading some to consider diet a relatively ineffective therapy (6). However, recent developments have suggested that the traditional focus of lipid management may have been overly simplistic and that diets might be more effective if more attention was focused on including certain foods or factors rather than just avoiding saturated fat and cholesterol. Effective refinements of dietary strategies for lipid management could decrease the gap in effectiveness between dietary approaches and drug therapy. Several dietary factors or foods, including soy protein, soy isoflavones, plant sterols, soluble fiber, oats, nuts, and garlic, have established or potential lipid benefits (7-13). Each is derived from plant food sources, and it is inclusion of these factors, rather than avoidance, that is reported to confer benefits. However, given that most plant foods contain low or negligible amounts of saturated fat and that all plant foods are devoid of cholesterol, it follows that a plant-based diet is inherently low in saturated fat and cholesterol. Therefore, it is difficult to distinguish between plasma lipid benefits derived from the actual plant-based dietary components and those derived from avoidance of saturated fat and cholesterol. Several studies have been designed to test the effects on plasma lipids of diets with identical saturated fat and cholesterol intake but varied amounts of 1 or 2 additional dietary components (14-16). Data are more limited on dietary approaches that hold saturated fat and cholesterol intake constant while modifying multiple other dietary components simultaneously (17). Modifying multiple dietary components simultaneously (for example, increasing intake of vegetables, fruits, and low-fat dairy) while holding sodium intake constant has been shown to effectively lower elevated blood pressure in the Dietary Approaches to Stop Hypertension trials (DASH I and II) (18, 19). Testing a parallel approach to refining dietary intervention for lipid management is warranted. In 2000, the American Heart Association (AHA) reported revised dietary guidelines that substantially modified its 1993 and 1996 guidelines (2, 4, 5). All 3 versions of the guidelines recommended keeping saturated fat intake at less than 10% of energy and cholesterol intake below 300 mg/d. A notable modification of the 2000 guidelines was to emphasize foods and overall eating patterns, including increased intakes of vegetables and whole grains (in general, a plant-based diet). It was our hypothesis that a plant-based diet consistent with the revised AHA 2000 guidelines would increase the LDL cholesterol-lowering benefits of the previous AHA Step I guidelines. We theorized that this improvement would be independent of the plant-based diets saturated fat and cholesterol content. Therefore, we designed 2 diets that had identical levels of total fat (30% of energy), saturated fat (10% of energy), and cholesterol (<300 mg/d) but differed substantially in content of nutrient- and phytochemical-dense plant-based foods. The purpose of the study was to determine whether LDL cholesterol-lowering benefits among adults with moderately elevated cholesterol levels would be greater under weight-stable conditions with a plant-based low-fat diet than with a more typical, convenience-oriented low-fat diet that was identical in intake of total fat, saturated fat, and cholesterol. Methods Participants Participants were recruited from the local community, primarily through newspaper advertisements, letters to previous study participants, and flyers sent to university employees. Men and women were invited to enroll if they were 30 to 65 years of age with fasting plasma LDL cholesterol levels of 3.3 to 4.8 mmol/L (130 to 190 mg/dL), fasting plasma triglyceride levels less than 2.83 mmol/L (< 250 mg/dL), body mass index between 19 and 31 kg/m2, and a current diet estimated to derive at least 10% of energy from saturated fat. Pregnant women, persons who smoked, persons with prevalent heart disease or diabetes, or persons who had been using lipid-lowering or blood pressure-lowering medications within the past month (all determined through self-report) were excluded. During the recruitment phase, 1096 individuals were screened by telephone interview and 345 who met the initial inclusion criteria were considered eligible for cholesterol testing. Of these 345 persons, 188 who were found to have eligible concentrations of LDL cholesterol and triglycerides attended an orientation meeting. Fifty-one persons decided not to participate (primarily because of the time commitment), and an additional 12 potential participants were excluded after a 3-day food record showed that their estimated average intake of saturated fat was already less than 10% of energy. One hundred twenty-five participants were randomly assigned to 1 of the 2 diet groups. The Stanford University Human Subjects Committee reviewed and approved the investigation, all participants signed an informed consent form before enrollment, and the study was performed according to Declaration of Helsinki guidelines (20). Design The trial used a parallel design. We randomly assigned participants in blocks of 20 by selecting, without replacement, from a set of indistinguishable envelopes containing 10 assignments to each of the 2 diet groups. Randomization of the envelopes was done by hand, without a computer algorithm. No stratification criteria were used. Each participant was provided with meals, snacks, and beverages on an outpatient basis for 28 days, as described later. Diets Both study diets were designed to provide 30% of energy from total fat, 10% of energy from saturated fat, and approximately 100 mg of cholesterol per 1000 kcal per day. During the menu-designing stage of the study, the nutrient composition of the diets was determined by using the database of Food Processor software, version 7.0 (ESHA Research, Salem, Oregon). Menus were designed by using commonly available foods from local markets. The Low-Fat diet was designed to include many reduced-fat prepared-food items (for example, reduced-fat cheeses, low-fat frozen lasagna, and low-fat and sugar-rich snack foods). In contrast, the Low-Fat Plus diet was designed to include considerably more vegetables, legumes, whole grains, and fruits. Butter, cheese, and eggs were added to the daily menus for the Low-Fat Plus diet, increasing the saturated fat and cholesterol content to match the Low-Fat diet. A 7-day menu cycle was designed for each of the 2 study diets; therefore, each menu was repeated 4 times during the 28 days. The diets included breakfast, lunch, dinner, beverages, and snacks for each day. Each weekday, the participants ate either lunch or dinner at the dining facility of the Stanford General Clinical Research Center. After their on-site meal, they were given coolers that contained meals and snacks to be consumed off-site. On Fridays, participants received weekend meals to be consumed off-site. Appendix Table 1 and Appendix Table 2 list the daily menus. One free-choice evening meal was allowed each weekend. For this meal, participants were given guidelines for choosing low-fat meals consistent with their diet assignments and were required to keep a record of foods consumed. These records were analyzed for nutritional content and were used to determine the impact of the free-choice meals on the overall study diets. Adherence was measured by using daily log sheets kept by participants that tracked incomplete consumption of study foods or consumption of any nonstudy foods. The 28 daily food logs for each participant were examined for deviations from the diets. The energy contribution of each deviation was determined and then totaled for the entire 28-day protocol period. Each of the 14 daily menus (7-day cycle 2 diets) was analyzed chemically for nutrient content before the study and then again during the study (Covance Laboratories, Madison, Wisconsin). The chemical analyses performed before the study confirmed that the average composition of the daily menus provided 30% of energy from total fat, 10% of energy from saturated fat, and approximately 100 mg of cholesterol per 1000 kcal per day. When the 2 diets were first designed, we attempted to match their mono- and polyunsaturated fat content. However, the database used in the design phase was missing values for these nutrients for approximately 20% of the foods. In addition, many of the specific products purchased locally for the study provided incomplete information for the content of these unsaturated fats. The first round of chemical analyses of the diets, performed before enrollment began, indicated a modest discrepancy b

The insulin resistance syndrome and coronary artery disease.

&NA; Insulin resistance is an increasingly common metabolic abnormality characterized by an impaired physiological response to insulin. The constellation of insulin resistance and several other metabolic and vascular disorders is known as the insulin resistance syndrome. The characteristic features of the insulin resistance syndrome include central obesity, hypertension, dyslipidemia, glucose intolerance and specific abnormalities of both endothelial cell and vascular function. Although insulin resistance can arise in response to aging, obesity and inactivity, there is a clear genetic component. Insulin resistance is not generally attributable to a single genetic defect. Indeed, it is very likely to be a polygenic disorder in most individuals. A genetic predisposition is suggested to be the demonstration of increased insulin resistance in first‐degree relatives of patients with diabetes and by a high incidence of insulin resistance in specific populations. Epidemiological data have demonstrated a strong association between a clustering of specific factors and the risk of cardiovascular disease. The diagnosis of the insulin resistance syndrome remains a significant clinical challenge. At present, clinicians are faced with establishing a clinical diagnosis despite varying definitions of the disorder and controversy regarding how many components presage clinical events. A proposed approach to the management of patients with the insulin resistance syndrome is discussed. Coron Artery

Comparison of Metabolic Effects of White Beans Processed Into Two Different Physical Forms

In the present study eight control subjects and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) consumed single portions of processed beans equivalent to 50 g of carbohydrate. The beans were processed by different methods into two physical forms; one maintained the integrity of the bean cells (undamaged bean cells, UC) and the other ruptured the bean cells (damaged bean cells, DC). Incremental glucose response areas after ingestion of either UC or DC were not significantly different in control subjects, while incremental insulin response areas (49 ± 7 vs. 26 ± 4 μU · ml−1 · h−1 P < .05) were significantly lower after eating UC-processed beans. In patients with NIDDM both incremental glucose (150 ± 14 vs. 73 ± 25 mg · dl−1 · h - 1 ,P < .001) and insulin (67 ± 16 vs. 46 ± 11 μU · ml−1 · h−1 P < .05) response areas were significantly lower after UC administration. To test the effectiveness of the UC-processed bean when incorporated into mixed meals, nine patients with NIDDM consumed mixed meals containing either DC or UC on two separate mornings. The test meals represented a typical Mexican American use of pureed beans wrapped in a flour tortilla topped with melted cheese. Incremental glucose responses were significantly lower after the UC meal (171 ± 42 mg · dl−1 · h−1 P < .05) when compared with the DC meal (212 ± 34 mg · dl−1 · h−1). Incremental insulin areas were also lower after the UC (91 ± 19 μU · ml−1 · h−1) when compared with the DC meal (120 ± 22 μU · ml−1 · h−1). Our study demonstrates that consumption of white beans prepared in a manner that maintains the integrity of the cells profoundly modified the ensuing plasma glucose and insulin response in patients with NIDDM as compared with white beans milled in a more conventional fashion. Moreover, the lower glucose and insulin response to UC beans occurred when the beans were consumed alone or in a mixed meal and suggests that the practice of processing carbohydrate-rich foods in a manner that leaves the food form intact may be of significant clinical importance.