Vladimir Vuksan

Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the study of health assessment and risk in ethnic groups (SHARE)

Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese and Europeans. A total of 985 participants were recruited from three cities (Hamilton, Toronto and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured. Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5% and 2%, respectively; p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm) and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and low-density lipoprotein cholesterol, higher triglycerides and lower high-density lipoprotein cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein(a), and plasminogen activator inhibitor-1. Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.

Defining Obesity Cut Points in a Multiethnic Population

Background— Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m2) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans. Methods and Results— We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or “hidden” factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure–related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by ≈6 kg/m2 among non-European groups compared with Europeans. Conclusions— Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.

Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

Hyperbolic Relationship Between Insulin Secretion and Sensitivity on Oral Glucose Tolerance Test

The utility of the disposition index as a measure of β‐cell compensatory capacity rests on the established hyperbolic relationship between its component insulin secretion and sensitivity measures as derived from the intravenous glucose tolerance test (IVGTT). If one is to derive an analogous measure of β‐cell compensation from the oral glucose tolerance test (OGTT), it is thus necessary to first establish the existence of this hyperbolic relationship between OGTT‐based measures of insulin secretion and insulin sensitivity. In this context, we tested five OGTT‐based measures of secretion (insulinogenic index, Stumvoll first phase, Stumvoll second phase, ratio of total area‐under‐the‐insulin‐curve to area‐under‐the‐glucose‐curve (AUCins/gluc), and incremental AUCins/gluc) with two measures of sensitivity (Matsuda index and 1/Homeostasis Model of Assessment for insulin resistance (HOMA‐IR)). Using a model of log(secretion measure) = constant + β × log(sensitivity measure), a hyperbolic relationship can be established if β is approximately equal to −1, with 95% confidence interval (CI) excluding 0. In 277 women with normal glucose tolerance (NGT), the pairing of total AUCins/gluc and Matsuda index was the only combination that satisfied these criteria (β = −0.99, 95% CI (−1.66, −0.33)). This pairing also satisfied hyperbolic criteria in 53 women with impaired glucose tolerance (IGT) (β = −1.02, (−1.72, −0.32)). In a separate data set, this pairing yielded distinct hyperbolae for NGT (n = 245) (β = −0.99, (−1.67, −0.32)), IGT (n = 116) (β = −1.18, (−1.84, −0.53)), and diabetes (n = 43) (β = −1.37, (−2.46, −0.29)). Moreover, the product of AUCins/gluc and Matsuda index progressively decreased from NGT (212) to IGT (193) to diabetes (104) (P < 0.001), consistent with declining β‐cell function. In summary, a hyperbolic relationship can be demonstrated between OGTT‐derived AUCins/gluc and Matsuda index across a range of glucose tolerance. Based on these findings, the product of these two indices emerges as a potential OGTT‐based measure of β‐cell function.

Physiological Effects of Resistant Starches on Fecal Bulk, Short Chain Fatty Acids, Blood Lipids and Glycemic Index

OBJECTIVE To assess the effects on fecal bulking, fecal short chain fatty acid (SCFA) production, blood lipids and glycemic indices of two different forms of resistant starch (RS2 and RS3) from a high-amylose cornstarch. METHODS Twenty-four healthy subjects (12 men; 12 women) consumed four supplements taken for 2 weeks in random order separated by 2-week washout periods. The supplements were a low-fiber (control) and supplements providing an additional 30 g dietary fiber as wheat bran (high-fiber control) or the equivalent amount of resistant starch analyzed gravimetrically as dietary fiber from RS2 or RS3. Four-day fecal collections and 12-hour breath gas collections were obtained at the end of each period. Fasting blood was taken at the beginning and end of each period. Glycemic indices of supplements were also assessed. RESULTS The wheat bran supplement increased fecal bulk 96+/-14 g/day compared with the low-fiber control (p<0.001) with the mean for both resistant starches also being greater (22+/-8 g/day) than the low-fiber control (p=0.013). On the resistant starch phases, the mean fecal butyrate:SCFA ratio, which has been suggested to have positive implications for colonic health, was significantly above the low-fiber control by 31+/-14% (p=0.035). Resistant starches did not alter serum lipids, urea or breath H2 or CH4. No significant differences in glycemic index were seen between the RS and control supplements. CONCLUSION The potential physiological benefits of the resistant starches studied appear to relate to colonic health in terms of effects on fecal bulk and SCFA metabolism.

Beneficial Effect of Low-Glycemic Index Diet in Overweight NIDDM Subjects

Objectives To determine whether low-glycemic index (GI) diets have clinical utility in overweight patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods Six patients with NIDDM were studied on both high- and low-GI diets of 6-wk duration with metabolic diets with a randomized crossover design. Both diets were of similar composition (57% carbohydrate, 23% fat, and 34 g/day dietary fiber), but the low-GI diet had a GI of 58 compared with 86 for the high-GI diet. Results Small and similar amounts of weight were lost on both diets: 2.5 kg on high-GI diet and 1.8 kg on low-GI diet. On the low-GI diet, the mean level of serum fructosamine, as an index of overall blood glucose control, was lower than on the high-GI diet by 8% (P <0.05), and total serum cholesterol was lower by 7% (P <0.01). Conclusions In overweight patients with NIDDM, reducing diet GI improves overall blood glucose and lipid control.

Beneficial Effect of a Low Glycaemic Index Diet in Type 2 Diabetes

Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects, and improve blood glucose control in Type 1 and well‐controlled Type 2 diabetic patients. We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol I−1 using a randomized, crossover design. Patients were given pre‐weighed diets (59% energy as carbohydrate, 21% fat, and 24g 1000‐kcal−1 dietary fibre) for two 2‐week periods, with a diet glycaemic index of 60 during one period and 87 during the other. On the low glycaemic index diet, the blood glucose response after a representative breakfast was 29% less than on the high glycaemic index diet (874 ± 108 (± SE) vs ± 204 ± 112 mmol min I−1; p < 0.001), the percentage reduction being almost identical to the 28% difference predicted from the meal glycaemic index values. After the 2‐week low glycaemic index diet, fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet (3.17 ± 0.12 vs 3.28 ± 0.16 mmol I−1 p < 0.05, and 5.5 ± 0.4 vs 5.9 ± 0.5 mmol I−1, p < 0.02, respectively. Urinary C‐peptide excretion, as an index of insulin secretion, was 30% lower on the low than the high glycaemic index diet (2.05 ± 0.30 vs 2.93 ± 0.49 nmol mmol‐creatinine−1; p < 0.02), urinary urea was reduced by 19% (347 ± 27 vs 402 ± 39 mmol 24‐h−1; p < 0.025), consistent with enhanced colonic fermentation. These results suggest that low glycaemic index starchy foods may be beneficial in the treatment of Type 2 diabetes.

Inulin, Oligofructose and Intestinal Function

Inulin and oligofructose have attracted much attention recently as nonabsorbable carbohydrates with prebiotic properties. When inulin and oligofructose were added to a controlled diet, significant increases were noted in colonic bifidobacterial populations, and it has been proposed that these changes promote both colonic and systemic health through modification of the intestinal microflora. Inulin and oligofructose are rapidly and completely fermented by the colonic microflora with the production of acetate and other short-chain fatty acids. As with lactulose, they may also result in the growth of the fecal biomass, and in doing so, entrap ammonia for bacterial protein synthesis or conversion to the ammonium ion. As with dietary fiber and other nonabsorbable carbohydrates, there is also interest in inulin and oligofructose from the standpoint of inhibition of colonic carcinogenesis, blood cholesterol reduction, immune stimulation and enhanced vitamin synthesis. In these areas, the influence of their molecular weight is also an issue, with the longer chain length providing a more sustained fermentation pattern. More human studies are now required, including studies on the long-term effects of inulin and oligofructose consumption on colonic health, in particular on markers of cancer risk such as reduction in colonic polyp recurrence.

Glycaemic index of 102 complex carbohydrate foods in patients with diabetes

Abstract Low glycaemic index diets reduce blood glucose and lipid levels in humans but glycaemic index values are only available for a small number of foods. Thus, we determined the glycaemic index of 102 complex carbohydrate foods in patients with diabetes. The values varied from 37 for bean thread noodles to 127 for Rice Chex cereal (p

Metabolic effects of reducing rate of glucose ingestion by single bolus versus continuous sipping.

Modifying the rate of absorption has been proposed as a therapeutic principle of specific relevance to diabetes. To demonstrate clearly the metabolic benefits that might result from reducing the rate of nutrient delivery, nine healthy volunteers took 50 g glucose in 700 ml water on two occasions: over 5-10 min (bolus) and at a constant rate over 3.5 h (sipping). Despite similar 4-h blood glucose areas, large reductions were seen in serum insulin (54 +/- 10%, P less than 0.001) and C-peptide (47 +/- 12%, P less than 0.01) areas after sipping, together with lower gastric inhibitory polypeptide and enteroglucagon levels and urinary catecholamine output. There was also prolonged suppression of plasma glucagon, growth hormone, and free-fatty acid (FFA) levels after sipping, whereas these levels rose 3-4 h after the glucose bolus. An intravenous glucose tolerance test at 4 h demonstrated a 48 +/- 10% (P less than 0.01) more rapid decline in blood glucose (Kg) after sipping than after the bolus. Furthermore, FFA and total branched-chain amino acid levels as additional markers of insulin action were lower over this period despite similar absolute levels of insulin and C-peptide. These findings indicate that prolonging the rate of glucose absorption enhances insulin economy and glucose disposal.