Showing papers in "Diabetes Care in 1991"
TL;DR: In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
Abstract: Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
4,582 citations
TL;DR: It is hypothesized that free fatty acids and testosterone might provide a background not only to a defense reaction and primary hypertension, suggested previously, but also to a defeat reaction, which contributes to an endocrine aberration leading to metabolic aberrations and visceral fat accumulation, which in turn leads to disease.
Abstract: Insulin resistance is the cornerstone for the development of non-insulin-dependent diabetes mellitus (NIDDM). Free fatty acids (FFAs) cause insulin resistance in muscle and liver and increase hepatic gluconeogenesis and lipoprotein production and perhaps decrease hepatic clearance of insulin. It is suggested that the depressing effect of insulin on circulating FFA concentration is dependent on the fraction derived from visceral adipocytes, which have a low responsiveness to the antilipolytic effect of insulin. Elevated secretion of cortisol and/or testosterone induces insulin resistance in muscle. This also seems to be the case for low testosterone concentrations in men. In addition, cortisol increases hepatic gluconeogenesis. Cortisol and testosterone have “permissive” effect on adipose lipolysis and therefore amplify lipolytic stimulation; FFA, cortisol, and testosterone thus have powerful combined effects, resulting in insulin resistance and increased hepatic gluconeogenesis. All these factors promoting insulin resistance are active in abdominal visceral obesity, which is closely associated with insulin resistance, NIDDM, and the “ metabolic syndrome.” In addition, the endocrine aberrations may provide a cause for visceral fat accumulation, probably due to regional differences in steroid-hormone-receptor density. In addition to the increased activity along the adrenocorticosteroid axis, there also seem to be signs of increased activity from the central sympathetic nervous system. These are the established endocrine consequences of hypothalamic arousal in the defeat and defense reactions. There is some evidence that suggests an increased prevalence of psychosocial stress factors is associated with visceral distribution of body fat. Therefore, it is hypothesized that such factors might provide a background not only to a defense reaction and primary hypertension, suggested previously, but also to a defeat reaction, which contributes to an endocrine aberration leading to metabolic aberrations and visceral fat accumulation, which in turn leads to disease.
1,033 citations
TL;DR: Joint mobility was reduced at both sites in groups 1 and 2 compared with groups 3, 4, and 5, and LJM contributes to foot ulceration in the susceptible neuropathic foot.
Abstract: Objective To investigate the role of limited joint mobility (LJM) in causing abnormal foot pressures and foot ulceration. Research Design and Methods The subjects were recruited from a general diabetes clinic where patients were screened for neuropathy, retinopathy, and elevated plantar foot pressure. Sixty-four patients in five groups were matched by age and sex in the following groups: group 1, patients with LJM and neuropathy; group 2, nonneuropathic diabetic patients with LJM; group 3, patients with neuropathy and no LJM; group 4, diabetic control subjects; and group 5, nondiabetic control subjects. Joint mobility was assessed in the foot at subtalar and metatarsophalangeal joints; plantar foot pressures were assessed by optical pedobarography and neuropathic status by a Biothesiometer and electrophysiology. Results Joint mobility was reduced at both sites in groups 1 and 2 compared with groups 3, 4, and 5 ( P P r = −0.7, P Conclusions 1) LJM may be a major factor in causing abnormally high plantar foot pressures, 2) abnormal plantar foot pressures alone do not lead to foot ulceration, and 3) LJM contributes to foot ulceration in the susceptible neuropathic foot.
352 citations
TL;DR: Perturbations in mineral metabolism are more pronounced in diabetic populations with specific complications, and differences in trace element status are a consequence of diabetes, or alternatively, whether they contribute to the expression of the disease.
Abstract: Objective To evaluate copper, zinc, manganese, magnesium, and other indices of peroxidative status in diabetic and nondiabetic human subjects. Research Design and Methods Convenience sample of 57 insulin-dependent or non-insulin-dependent diabetic subjects recruited from the diabetes clinic of the University of California, Davis, Medical Center and 28 nondiabetic subjects recruited from the staffs of the Departments of Internal Medicine and Nutrition. Individuals conducting laboratory analyses were blind to subject group. A fasting blood sample was collected from all subjects and appropriately processed for future analyses. A 24-h urine collection was obtained in a subset of subjects. Results Hyperzincuria and hypermagnesuria were evident in diabetic subjects compared with control subjects. There were no differences in plasma magnesium or whole-blood manganese between groups. Plasma copper was higher and plasma zinc was lower in diabetic than in control subjects. When data were viewed with respect to specific diabetes-associated complications, diabetic subjects with retinopathy, hypertension, or microvascular disease had higher plasma copper concentrations compared with both diabetic subjects without complications and with control subjects. There were no significant differences between control and diabetic subjects in erythrocyte copper-zinc superoxide dismutase activity or whole-blood glutathione peroxidase or glutathione reductase activities. Plasma peroxide concentrations were higher in diabetic than control subjects. Conclusions Diabetes can alter copper, zinc, magnesium, and lipid peroxidation status. Perturbations in mineral metabolism are more pronounced in diabetic populations with specific complications. It is not known whether differences in trace element status are a consequence of diabetes, or alternatively, whether they contribute to the expression of the disease.
336 citations
TL;DR: Resistance to insulin action on glucose uptake in peripheral tissues is a common underlying mechanism in hypertension and diabetes and may explain the unexpectedly high incidence of the development of diabetes among treated hypertensives and the poor effect on risk for coronary heart disease in intervention trials.
Abstract: The close relationship between diabetes and hypertension has been recognized for decades. New information indicates that resistance to insulin action on glucose uptake in peripheral tissues is a common underlying mechanism in hypertension and diabetes. In prospective trials, the effects of antihypertensive agents on insulin sensitivity and lipoprotein metabolism have been evaluated. Both beta-blockers and thiazide diuretics worsen insulin resistance and deteriorate lipoprotein metabolism. Angiotensin-converting enzyme (ACE) inhibitors, Ca2(+)-channel blockers, and alpha-blockers are neutral or improve these factors. These data may explain the unexpectedly high incidence of the development of diabetes among treated hypertensives and the poor effect on risk for coronary heart disease in intervention trials.
331 citations
TL;DR: There is evidence that the changes in glucose, insulin, and lipoprotein metabolism may play a role in the etiology and/or clinical course of patients with high blood pressure and an effort is made to marshal the evidence in support of the latter alternative.
Abstract: There is considerable evidence that abnormalities of glucose, insulin, and lipoprotein metabolism occur more frequently in untreated hypertensive patients than in normotensive control subjects. More recently, it has also become apparent that similar metabolic abnormalities occur in rodent models of hypertension. One purpose of this article is to review the experimental data that have led to the above generalizations. The second goal is to address the significance of these findings, which is certainly not clear. For example, it could be argued that the relationship between high blood pressure and the associated metabolic defects is incidental. On the other hand, there is evidence that the changes in glucose, insulin, and lipoprotein metabolism may play a role in the etiology and/or clinical course of patients with high blood pressure. Although it is impossible at this point to definitively choose between these possibilities, an effort is made to marshal the evidence in support of the latter alternative.
316 citations
TL;DR: A low-GI diet gives a modest improvement in long-term glycemic control but not plasma lipids in normolipidemic well-controlled subjects with NIDDM.
Abstract: Objective To compare high- and low-glycemic index (GI) diets in the treatment of non-insulin-dependent diabetes mellitus (NIDDM).
Research Design and Methods Sixteen subjects with well-controlled NIDDM and normal lipid profile, 10 of whom continued oral hypoglycemic medication, participated in the study. A diet that emphasized low-GI foods (e.g., porridge, pasta) was compared with a high-GI diet (e.g., processed cereals, potatoes). The GI of the low-GI diet was 15% lower than the high-GI diet (77 ± 3 vs. 91 ± 1) but otherwise similar in macronutrient composition and fiber, as determined by a 4-day weighed record. The diets were instituted under instruction from a dietitian who visited subjects at home on a weekly basis. Body weight was maintained within 1–2 kg.
Results Glycemic control was improved on the low-GI diet compared with the high-GI diet (statistically significant findings, P < 0.05). Mean glycosylated hemoglobin at the end of the low-GI diet was 11% lower (7.0 ± 0.3%) than at the end of the high-GI diet (7.9 ± 0.5%), and the 8-h plasma glucose profile was lower (area under the curve above fasting 128 ± 23 vs. 148 ± 22 mmol.h-1.L-1, respectively). Mean fasting plasma glucose, total cholesterol triglycerides, and lipoproteins did not show important differences.
Conclusions A low-GI diet gives a modest improvement in long-term glycemic control but not plasma lipids in normolipidemic well-controlled subjects with NIDDM.
315 citations
TL;DR: The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976–1980 and the total prevalence was significantly lower for Cubans.
Abstract: The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non-Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982-1984. The interviewed sample of people aged 20-74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976-1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45-74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors.
303 citations
TL;DR: The role of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of non-insulin-dependent (NIDDM) diabetes mellitus are complex and require further investigation as mentioned in this paper.
Abstract: Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
276 citations
TL;DR: It is demonstrated that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile gly cosylation, the first step of the Maillard reaction.
Abstract: Objective This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. Research Design and Methods Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA 1 , and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients. Results Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA 1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA 1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA 1 levels, stable HbA 1 , and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration. Conclusions These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.
257 citations
TL;DR: Attributable risk fractions for Mauritius suggest that populationwide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM (and IGT) and interventions should be attempted in high-risk populations.
Abstract: Objective We wanted to determine whether obesity, abdominal fat distribution, and physical inactivity act similarly and independently as risk factors for noninsulin- dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in Hindu and Muslim Asian Indians, African-origin Creoles, and Chinese Mauritians. Research Design and Methods We examined a population-based random cluster sample of 5080 adult subjects from the Indian Ocean island of Mauritius. Glucose tolerance was assessed with a 75-g oral glucose tolerance test and World Health Organization criteria. Results Univariate data and multiple logistic regression models indicated that age, family history of diabetes, body mass index (BMI), waisthip ratio (WHR), and physical inactivity conveyed similar risk for NIDDM (and IGT) in each ethnic group. After adjusting for all other factors, Hindu ethnicity conferred additional risk for NIDDM (but not IGT) in men, but in women there were no clear ethnic differences. Although BMI and WHR were independently significant risk factors, WHR conveyed relatively stronger risk for NIDDM than BMI in women, whereas the converse was true in men. For ethnic groups combined, the independent odds ratios for IGT associated with moderate and low physical activity scores (relative to high) were 1.56 and 1.71 ( P P P P Conclusions These data indicate that BMI, abdominally distributed fat, and physical inactivity are important independent risk factors for both IGT and NIDDM in diverse ethnic groups. Attributable risk fractions for Mauritius suggest that populationwide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM (and IGT). Such interventions should be attempted in high-risk populations.
TL;DR: It is suggested that, in an elderly population, the habitual consumption of a small amount of fish may protect against the development of impaired glucose tolerance and diabetes mellitus.
Abstract: Objective To examine the association of fish intake with the subsequent risk of impaired glucose tolerance and diabetes mellitus (glucose intolerance). Research Design and Methods In 1971, information about food intake was obtained by the cross-check dietary history method on 175 men and women aged 64-87 yr who were normoglycemic and free of clinical diabetes. During the follow-up period from 1972 to 1975, an oral glucose tolerance test was performed annually, and in 59 of 175 elderly people a diagnosis of glucose intolerance was made at least once. Results In 1971, ~ 60% of the subjects usually ate fish, with a mean daily intake of 24.2 g. In fish eaters, the incidence of glucose intolerance was significantly lower compared with nonfish eaters (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.21-0.77). With logistic regression analysis, this inverse association could not be explained by taking into account age and sex or possible confounding baseline characteristics, such as the prevalence of myocardial infarction, body mass index, energy intake per kilogram body weight, or intake of carbohydrates (OR 0.47, 95% CI 0.23-0.93). Baseline characteristics of the oral glucose tolerance test and serum triglyceride levels could also not account for this result. Conclusions These results suggest that, in an elderly population, the habitual consumption of a small amount of fish may protect against the development of impaired glucose tolerance and diabetes mellitus.
TL;DR: The epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk.
Abstract: The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) risk factors in a large population of working men. The baseline cohort included 7028 men, 6093 who had a 75-g oral glucose tolerance test with measurement of plasma insulin and glucose levels (0 and 2 h) and 125 who were known non-insulin-treated diabetic patients. After a mean follow-up of 11 yr, 126 deaths ascribed to CHD were reported. Major independent predictors of CHD death were blood pressure, smoking, plasma cholesterol level, and fasting and 2-h postload plasma insulin level. Impairment of glucose tolerance, including overt diabetes, did not rank as an independent predictor when other baseline variables were accounted for. In the subset of the baseline cohort who presented with impaired glucose tolerance or diabetes (n = 943), 26 died from CHD during the follow-up. The strongest independent predictor of subsequent CHD death in this subsample with abnormal glucose tolerance was plasma triglyceride level. In view of the accumulating evidence that hyperinsulinemia and hypertriglyceridemia generally occur in the same type of subjects, in relation to insulin resistance and central obesity, the epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk.
TL;DR: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.
Abstract: Objective To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods Nineteen NIDDM patients (mean ± SD age 48.9 ± 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (> 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. Results The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA 1c decreased ( n = 19, FPG, 11.0 ± 2.4 vs. 8.4 ± 2.7 mM [before vs. after], P 1c , 8.0 ± 1.1 vs. 7.4 ± 1.3%, P n = 19, fasting IRI, 77.4 ± 49.8 vs. 56.5 ± 24.6 pM [before vs. after], P P Conclusions CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.
TL;DR: These trials showed that β-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca2+ - channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral.
Abstract: In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension.
TL;DR: A professional education program designed to facilitate the acquisition and enhancement of the requisite skills and attitudes was designed, implemented, and evaluated.
Abstract: The patient empowerment approach to diabetes education is intended to enable patients to make informed decisions about their own diabetes care and to be fully responsible members of the health-care team. Facilitating patient empowerment requires a specific set of skills and attitudes on the part of diabetes educators. A professional education program designed to facilitate the acquisition and enhancement of the requisite skills and attitudes was designed, implemented, and evaluated. The program involved adhering to a simulated diabetes care regimen for 3 days followed by a 3-day intensive skills-based workshop. The 23 educators who participated in the first two offerings of this program made significant gains in their counseling skills and demonstrated a positive change in attitude.
TL;DR: A balanced increase in consumption of fiber-rich foods and unsaturated fat is the most rational way to replace foods rich in saturated fat and cholesterol in the diabetic diet.
Abstract: Dietary recommendations for the treatment of diabetic patients issued by national and international diabetes associations consistently emphasize the need to increase carbohydrate consumption. However, these recommendations have been questioned on the basis of growing evidence that, in both insulin-dependent and non-insulin-dependent diabetic patients, a high-carbohydrate diet does not offer any advantage in terms of blood glucose and plasma lipid concentrations compared with a high-fat (mainly unsaturated) diet. It has been shown repeatedly that a high-carbohydrate diet increases plasma insulin and triglyceride levels and can deteriorate blood glucose control in the postprandial period. However, much of the controversy between advocates and detractors of dietary carbohydrate can be settled by taking into account dietary fiber. Several studies have shown that the adverse metabolic effects of high-carbohydrate diets are neutralized when fiber and carbohydrate are increased simultaneously in the diet for diabetic patients. In particular, these studies demonstrated that a high-carbohydrate/high-fiber diet significantly improves blood glucose control and reduces plasma cholesterol levels in diabetic patients compared with a low-carbohydrate/low-fiber diet. In addition, a high-carbohydrate/high-fiber diet does not increase plasma insulin and triglyceride concentrations, despite the higher consumption of carbohydrates. Unfortunately, dietary fiber represents a heterogenous category, and there is still much to understand as to which foods should be preferred to maximize the metabolic effects of fiber. There are indications that only water-soluble fiber is active on plasma glucose and lipoprotein metabolism in humans. Therefore, in practice, the consumption of legumes, vegetables, and fruits--rich in water-soluble fiber--should be particularly encouraged. The mechanisms by which dietary fiber exerts its hypoglycemic and hypolipidemic activities are unknown. However, the ability of dietary fiber to retard food digestion and nutrient absorption certainly has an important influence on lipid and carbohydrate metabolism. The beneficial effects of high-fiber foods are also exerted by some foods not particularly rich in fiber. The fiber content and physical form of the food can influence the accessibility of nutrients by digestive enzymes, thus delaying digestion and absorption. The identification of these foods with a low-glycemic response would help enlarge the list of foods particularly suitable for diabetic patients. In conclusion, a diet low in cholesterol and saturated fat should be recommended to all diabetic patients to prevent cardiovascular disease. A balanced increase in consumption of fiber-rich foods and unsaturated fat is the most rational way to replace foods rich in saturated fat and cholesterol in the diabetic diet.
TL;DR: The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology.
Abstract: The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implications of these origins in the context of diabetes risk. Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups, i.e., Mexican Americans, Puerto Ricans, and Cubans. The U.S. Census figures provided basic demographic information. Genetic marker data for ancestral populations were taken from a review of the literature and compendia. Genetic marker data for the Puerto Rican and Cuban populations were extracted from the literature. Genetic markers determined on ∼ 1000 randomly selected Mexican Americans from Starr County, Texas, were taken as representative of the Mexican-American population. The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents, of whom 62% were classified as Mexican, 13% as Puerto Rican, and the remaining 25% as Cubans and others. Various lines of evidence can be used to characterize the Hispanic population and its origins. These include ethnohistory, self-assessment of ancestry, surname distributions, speech and cultural characteristics, quantitative traits, and genetic structure. Genetic data were used to estimate the contribution of putative ancestral populations to the contemporary gene pool. For Mexican Americans, 31% of the contemporary gene pool is estimated to be Native American derived, whereas 61 and 8% are Spanish and African derived, respectively. In Puerto Rico, the percentage of contributions of Spanish, Native American, and African admixture to the population are 45, 18, and 37%, respectively. For Cuba, the parallel estimates are 62, 18, and 20%. The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology. Our results are consistent with the finding of the significant role of genes in determining risk.
TL;DR: Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone and has beneficial effects on postprandial hyperinsulinemia and postpr andial hypertriglyceridemia.
Abstract: Objecative Acarbose inhibits α-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. Therefore, its efficacy and acceptability as a first-line drug in non-insulin-dependent diabetes mellitus (NIDDM) insufficiently treated with diet alone was tested in a randomized double-blind placebo-controlled study. Research Design And Methods Ninety-four NIDDM subjects, aged 43–70 yr with average body mass index of 28 kg/m 2 and undergoing a pretreatment period of at least 3 mo with diet alone, were treated with 100 mg acarbose three times daily or placebo for 24 wk. The patients were recruited after a 4-wk screening period of dietary reinforcement. The inclusion limits for patients termed diet not satisfactory were fasting blood glucose (FBG) ≥ 7.8 mM and/or postprandial blood glucose (BG) ≥ 10 mM. Results FBG was lowered in the acarbose group from 9.8 to 8.4 mM and in the placebo group from 10.2 to 9.6 mM after 24 wk ( P = 0.007 vs. placebo). The most impressive therapeutic effect was a highly significant reduction of postprandial hyperglycemia for at least 5 h after the test meal (1-h postprandial BG with acarbose 10.4 mM and placebo 13.5 mM at 24 wk, P 1 (acarbose 8.65%, placebo 9.32%, P = 0.003). Whereas C-peptide and fasting serum insulin were not significantly affected by acarbose, postprandial insulin increment was ∼ 30% lower after 24 wk compared with placebo. Furthermore, acarbose significantly reduced 1-h postprandial triglyceride levels. After an initial phase of > 4 wk (when 76.6% in the acarbose group vs. 28% on placebo complained about flatulence, P Conclusions Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone. It has beneficial effects on postprandial hyperinsulinemia and postprandial hypertriglyceridemia.
TL;DR: The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.
Abstract: Objective We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). Research Design And Methods We studied 103 newly diagnosed diabetic children Results The risk of IDDM was decreased (P Conclusions The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother9s education.
TL;DR: The incidence of type II diabetes in Mexican Americans is greater than in non-Hispanic whites, a difference that is not explained by ethnic differences in obesity, age, or level of educational attainment.
Abstract: Objective To determine whether Mexican Americans have an increased incidence of non-insulin-dependent (type II) diabetes mellitus relative to non-Hispanic whites. Currently, no study has reported on the incidence of this disorder in Mexican Americans. Research Design and Methods We determined the 8-yr incidence of type II diabetes in 617 Mexican Americans and 306 non-Hispanic whites who participated in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Forty Mexican Americans (6.5%) and 6 non-Hispanic whites (2%) developed type II diabetes, as defined by World Health Organization criteria. The age-adjusted ethnic odds ratio (OR; Mexican Americans/non-Hispanic whites) for diabetes incidence was 8.13 (95% confidence interval [C1] 1.10–59.9) in men and 3.62 (95% CI 1.37–9.55) in women. We adjusted for age, sex, ethnicity, body mass index, and level of educational attainment with multiple logistic regression analyses. Results Mexican Americans continued to show a statistically significant increase in diabetes incidence (OR 2.72, 95% CI 1.02–7.28). Obesity and age were also positively related to diabetes incidence in this analysis ( P Conclusions The incidence of type II diabetes in Mexican Americans is greater than in non-Hispanic whites, a difference that is not explained by ethnic differences in obesity, age, or level of educational attainment.
TL;DR: The most important finding was the significant increase of blood cholesterol in all three groups, which could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications.
Abstract: Objective In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). Research Design and Methods Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulindependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6- wk screening phase with conventional dietary treatment. During the follow-up, the control group ( n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group ( n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. Results Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P P P Conclusions IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.
TL;DR: The high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypglycemia are demonstrated, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient.
Abstract: Objective This study allocated the symptoms identified during acute hypoglycemia objectively to the autonomic or neuroglycopenic groups of symptoms by the use of factor analysis.
Research Design and Methods Twenty-five nondiabetic subjects, 14 newly diagnosed insulin-dependent diabetic patients, and 16 insulin-dependent diabetic patients with diabetes > 4 yr duration were studied. Acute hypoglycemia was induced with insulin (2.5 mU·kg−1 body wt·min−1 i.v.), and symptoms of hypoglycemia were recorded with a seven-point scale at regular time points throughout the studies. Factor analysis of the symptom scores at the time of the acute autonomic reaction with principal component analysis followed by Varimax rotation was used to separate those symptoms that might belong to neuroglycopenic and autonomic groups.
Results Hypoglycemia was induced to a mean ± SE plasma glucose nadir of 1.3 ± 0.1 mM in nondiabetic subjects, to 2.0 ± 0.3 mM in newly diagnosed diabetic patients, and 1.4 ± 0.2 mM in patients with diabetes of > 4 yr duration. The most frequently reported autonomic symptoms were sweating, trembling, and warmness, and the most frequently reported neuroglycopenic symptoms were inability to concentrate, weakness, and drowsiness. Neuroglycopenic symptoms were reported more commonly at the onset of hypoglycemia, which was identified by the development of symptoms. Factor analysis grouped trembling, anxiety, sweating, warmness, and nausea together, and this grouping was labeled an autonomic factor. A second factor was identified that included dizziness, confusion, tiredness, difficulty in speaking, shivering, drowsiness, and inability to concentrate, which was labeled a neuroglycopenic factor.
Conclusions This study demonstrated the high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypoglycemia, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient. Factor analysis assisted with the allocation of symptoms to either the autonomic or neuroglycopenic groupings, but the allocation of some symptoms remained undefined, and care must be taken when assessing symptoms such as hunger, weakness, blurred vision, and drowsiness when comparing the frequency of autonomic versus neuroglycopenic symptoms. To reduce the confusion resulting from the use of different symptom questionnaires in studies of hypoglycemia, a sample questionnaire is presented, the development of which was assisted by our analysis.
TL;DR: The findings suggest that the risk of coronary heart disease morbidity and mortality attributable to diabetes may be increasing over time and clinicians need to take extra care in the management of MIs in diabetic individuals.
Abstract: Objective The purpose of this study was to document trends in the prevalence of diabetes among men and women hospitalized for myocardial infarction (MI) and to determine the effect of diabetes on in-hospital case fatality rates and long-term survival. Research Design and Methods: The Minnesota Heart Survey is a population-based surveillance system that has monitored trends in coronary heart disease morbidity since 1970. As part of this effort, a 50% random sample of acute Ml discharge records in Minneapolis-St. Paul metropolitan area hospitals was abstracted in 1970,1980, and 1985.
Research Design and Methods The Minnesota Heart Survey is a population-based surveillance system that has monitored trends in coronary heart disease morbidity since 1970. As part of this effort, a 50% random sample of acute MI discharge records in Minneapolis-St. Paul metropolitan area hospitals was abstracted in 1970, 1980, and 1985.
Results The prevalence of diabetes among MI patients was compared over time, and the data indicated a significant increase between 1970 and 1985 in both men (8.2 vs. 16.8%, P = 0.001) and women (16.0 vs. 25.8%, P = 0.01). Diabetic individuals had an odds ratio of in-hospital death after an MI 1.5 times that of nondiabetic individuals ( P < 0.01) after controlling for the effects of sex, age, and year of MI. Among discharged MI survivors, the risk of death was 40% higher ( P < 0.01) in diabetic individuals than nondiabetic individuals after 6 yr of follow-up. Compared with nondiabetic individuals, diabetic individuals appeared more likely to have cardiac (pump) failure with acute MI.
Conclusions Our findings suggest that the risk of coronary heart disease morbidity and mortality attributable to diabetes may be increasing over time. Therefore, clinicians need to take extra care in the management of MIs in diabetic individuals, and public health efforts to reduce diabetes prevalence are warranted.
TL;DR: Investigation of NIDDM among Hispanics, blacks, and whites aged 20–74 yr in the United States population found increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence.
Abstract: Characteristics, prevalence, and risk factors for non-insulin-dependent diabetes mellitus (NIDDM) among Hispanics, blacks, and whites aged 20-74 yr in the United States population were investigated with two national surveys that used a household interview to ascertain diagnosed diabetes and a 75-g 2-h oral glucose tolerance test to measure undiagnosed diabetes. The Hispanic Health and Nutrition Examination Survey of 1982-1984 studied Mexican Americans in the southwest U.S., Cuban Americans in the Miami, Florida, area, and Puerto Ricans in the New York City area. The National Health and Nutrition Examination Survey of 1976-1980 examined a national sample of U.S. residents, of whom data on blacks and whites were analyzed. People with diagnosed diabetes in the five populations were similar with respect to mean age (53-57 yr), age at diagnosis (45-48 yr), duration of diabetes (6.9-8.7 yr), and diabetes therapies (58-67% using pharmacological treatment). Mean age of people with undiagnosed diabetes (51-59 yr) was comparable to that of diagnosed cases, and mean fasting (7.1-7.8 mM) and 2-h postchallenge plasma glucose (14.1-15.5 mM) values for people with undiagnosed diabetes were similar among the five populations. However, obesity levels varied by race, sex, and whether diabetes was diagnosed or undiagnosed. Age-standardized prevalence of diabetes (sum of diagnosed and undiagnosed cases) was 6.2% in whites, 9.3% in Cubans, 10.2% in blacks, 13% in Mexican Americans, and 13.4% in Puerto Ricans. Thus, compared to whites, diabetes rates were 50-60% higher among Cubans and blacks and 110-120% higher among Mexican Americans and Puerto Ricans. Age-standardized rates of impaired glucose tolerance were similar among the five populations (10.3-13.8%). Increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence.
TL;DR: Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people.
Abstract: Information on the metabolic response in people with non-insulin-dependent diabetes mellitus (NIDDM) to ingested individual macronutrients is limited. Available information is reviewed herein. The major absorbed products of carbohydrate-containing foods are glucose, fructose, and galactose. The quantitative effect of these on the plasma glucose and insulin response is different for each. In addition, available data indicate that the glucose and particularly the insulin response is different from that in nondiabetic people. The quantitative effect of dietary proteins and fats on the circulating glucose and insulin concentrations in nondiabetic and NIDDM subjects also has been reviewed. Neither has a significant effect on the glucose concentration. Protein stimulates insulin secretion, and this is relatively more prominent in people with NIDDM. A strong synergistic interaction with glucose on insulin secretion is present, but this is absent in nondiabetic people. Ingested fat does not independently stimulate insulin secretion. However, when ingested with carbohydrate, it may have a considerable effect on the plasma glucose and/or insulin response to that carbohydrate, and the responses are different in nondiabetic and NIDDM subjects. This is probably not due to altered carbohydrate absorption. Intestinal hormones undoubtedly are playing a large role in the insulin secretory response in all of these studies, but this remains to be completely elucidated. Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people. In our opinion, much more information is required before dietary recommendations for NIDDM subjects can be made based on solid scientific data.
TL;DR: The hypothesis that cows' milk may contain a triggering factor for the development of insulin-dependent diabetes mellitus (IDDM) is supported.
Abstract: Objective To compare age-standardized incidence rates of diabetes in children 0–14 yr of age and cows9 milk consumption in various countries. Research Design and Methods Ecological correlation study. Only incidence rates from diabetes registries carefully validated by the Diabetes Epidemiology Research International Study Group were used-Finland, Sweden, Norway, Great Britain, Denmark, United States, New Zealand, Netherlands, Canada, France, Israel, and Japan. Data on fluid cows9 milk consumption in corresponding countries were obtained from the International Dairy Federation. Results Correlation between milk consumption and incidence of insulin-dependent diabetes mellitus (IDDM) was 0.96. The data fit a linear regression model, and analysis showed that 94% of the geographic variation in incidence might be explained by differences in milk consumption. Conclusions The results support the hypothesis that cows9 milk may contain a triggering factor for the development of IDDM.
TL;DR: In this paper, a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations was conducted.
Abstract: Objective To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans.
Research Design and Methods Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external γ-counting.
Results The mean ± SE initial fractional disappearance rates for the four preparations were 20.7 ± 1.9 (hexameric soluble human insulin), 44.4 ± 2.5 (dimeric analogue AspB10), 50.6 ± 3.9 (analogue AspB28), and 67.4 ± 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin ( P < 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 ( P < 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates ( r = −0.98, P < 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 ± 6.8; dimer 44.4 ± 2.5 from 0 to 2 h and 68.9 ± 3.5 from 2.5 h onward; and hexameric insulin 20.7 ± 1.9 from 0 to 2 h, 45.6 ± 5.0 from 2.5 to 5 h, and 70.6 ± 6.3 from 5 h onward.
Conclusions Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.
TL;DR: It is suggested that the addition of a patient activation intervention to a comprehensive diabetes management program may substantially enhance physical functioning among adults with diabetes mellitus.
Abstract: Objective To determine whether a short intervention to enhance patient information seeking and decision making during hospitalization results in improved metabolic control and functional status in patients with diabetes mellitus. Research Design and Methods A randomized clinical trial was conducted in which control patients received a comprehensive 3-day evaluation and educational program, whereas experimental patients received a 45-min patient activation intervention and a 1-h self-administered booster in addition to the program. Metabolic control and functional status were measured at baseline and 4 mo postdischarge. Results During their discharge discussions, experimental patients asked significantly more questions than control patients (7.4 vs. 3.0, P > .001) and 4 mo later reported significantly fewer physical limitations in activities of daily living than the control group ( P = 0.02). Improvement in metabolic control was statistically significant only for experimental patients ( P = 0.02), although their glycosylated hemoglobin levels were not significantly lower than control patients9 at follow-up. The intervention did not diminish physician satisfaction with patient interactions, although it may have increased physician frustration with responsibilities that competed with patient care. CONCLUSIONS These results suggest that the addition of a patient activation intervention to a comprehensive diabetes management program may substantially enhance physical functioning among adults with diabetes mellitus.
TL;DR: This review highlights these and other potentially antiatherogenic properties of marine lipids in diabetic subjects and several short-term clinical trials in which fish-oil concentrates have been administered to various populations at risk for coronary heart disease, including patients with diabetes mellitus.
Abstract: Fish oils exert important biological effects on several pathways predisposing to atherosclerosis. Epidemiological studies provided the initial evidence that omega-3 fatty acids may be the principal factor in fish oils responsible for these effects and have led to several short-term clinical trials in which fish-oil concentrates have been administered to various populations at risk for coronary heart disease, including patients with diabetes mellitus. omega-3 Fatty acids reduce serum lipids and lipoproteins, impair platelet aggregation, increase cell membrane fluidity, and lower blood pressure in humans. In this review, we highlight these and other potentially antiatherogenic properties of marine lipids in diabetic subjects.