Issues in management: the role of insulin in cardiovascular outcomes.
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Arteriosclerosis↗
Biomedical subjects
S M Haffner
Publications and source records attributed to S M Haffner.
Specific insulin and proinsulin concentrations in nondiabetic South Indians.
The study was performed to determine plasma levels of proinsulin (PI) and specific insulin (SI) in normoglycemic (NGT) Asian Indians and to assess the effect of obesity and impaired glucose tolerance (IGT) on these concentrations. Blood samples from 151 adult nondiabetic South Indian subjects were collected during an epidemiological survey of diabetes. Plasma SI and PI levels were measured in fasting and 30-minute and 120-minute samples of a glucose tolerance test (World Health Organization criteria) using monospecific antibodies. The total insulin (TI) level was also measured by the nonspecific assay. The molar ratio of PI to SI (PI/SI) was calculated. Correlations of the peptides with anthropometry, serum lipids, and blood pressure (BP) were studied by univariate and multivariate analyses. Comparisons were also made in NGT versus IGT groups. As expected, TI values were higher than SI values, but the patterns of response were similar for both. SI and PI responses in NGT were similar to the values found in Mexican-Americans who had a higher body mass index (BMI). Asian Indians were thus found to have a high SI response despite a low BMI. Obesity and IGT produced an increased response of both PI and SI, with normal PI/SI ratios thus showing an absence of hyperproinsulinemia in either condition. Fasting PI showed a strong association with serum triglycerides, and proinsulin at 120 minutes was associated with cholesterol. None of the peptides showed a correlation with BP. Using specific assays for insulin and PI, it is shown that Asian Indians with NGT have a hyperinsulinemic response despite a low BMI. Obesity and mild hyperglycemia in IGT produce a simultaneous increase in PI and SI with no alteration in the PI/SI ratio.
Adult↗
Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.
The study purpose was to explore the association between dyslipidemia and insulin resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in California, Texas, and Colorado. The study population for this analysis consisted of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45 to 64 years) without diabetes. The IRAS clinical examinations included lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled intravenous glucose tolerance (FSIGT) test. The results show a consistent relationship between insulin-mediated glucose disposal and dyslipidemia in African American, Hispanic, and non-Hispanic white men and women. Further, LDL size was inversely associated with insulin resistance in all three ethnic groups. These findings indicate that dyslipidemia is a fundamental part of the insulin resistance syndrome in all of the ethnic groups studied.
Adult↗
Ability of alternative indices of insulin sensitivity to predict cardiovascular risk: comparison with the "minimal model". Insulin Resistance Atherosclerosis Study (IRAS) Investigators.
INTRODUCTION: Although recognition of insulin sensitivity as a risk factor for cardiovascular disease is growing, a deeper understanding of its role is impeded by the cost and complexity of currently available measures. This report evaluates previously described alternative indices of insulin sensitivity with the goal of identifying a reliable, but logistically simpler, alternative. METHODS: Data from 1460 participants in the Insulin Resistance Atherosclerosis Study (IRAS) were used to assess the proportion of the relationship between a recognized measure of insulin sensitivity (Bergman's SI) and cardiovascular risk factors that is contained in each of nine alternative measures. RESULTS: A number of the alternative indices contained a substantial proportion of the information available in Bergman's SI. The Galvin's index and the homeostasis model were most promising. However, there remained a significant amount of the information in Bergman's SI that was not contained in any of the alternative indices. DISCUSSION: There are simpler alternative indices of insulin sensitivity for use in epidemiological studies, but each alternative is associated with some loss of information. It may be possible that this loss can be overcome with an increased sample size; however, using the alternative indices may also confound the assessment of insulin sensitivity with other underlying factors (i.e., hyperinsulinemia). The alternative indices are not recommended for the clinical assessment of insulin sensitivity for an individual patient or subject.
Cardiovascular Diseases↗
Leptin concentrations do not predict weight gain: the Mexico City Diabetes Study.
BACKGROUND: Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake and increase energy expenditure. In humans, leptin levels are correlated with body fat. In addition, leptin levels decline in subjects who lose weight. Yet few data exist on whether leptin levels predict weight change, except for a recent report suggesting that low leptin levels predict weight gain in very obese middle-aged Pima Indians. METHODS: We have examined the association between baseline leptin levels and subsequent weight gain over 3.25 y in 180 non-diabetic participants in the Mexico City Diabetes Study. RESULTS: At baseline, the correlation between leptin levels and body mass index (BMI) was 0.712 in men and 0.691 in women (both P < 0.001). Subjects were matched on age (+/- 2 y), gender and BMI (+/- 2 kg/m2) at baseline. Baseline BMI was 25.3 kg/m2 in men and 27.2 kg/m2 in women. Baseline leptin levels (ng/ml) did not predict weight gain in either men (weight gainers: 4.3; weight stable: 5.8; and weight losers: 5.2) or women (weight gainers: 17.4; weight stable: 17.7; and weight losers: 17.4). CONCLUSIONS: We conclude that baseline leptin levels did not predict weight change in moderately obese individuals.
Adult↗
Serum leptin, food intake and preferences for sugar and fat in obese women.
OBJECTIVE: To examine the association of leptin with food intake and preferences for sugar and fat in obese humans. METHOD: Food intake and preferences for sugar and fat were measured in 35 obese women by a four-day food record and three hedonic tests, respectively. RESULTS: High fasting serum leptin concentration adjusted for body fat mass and dietary underreporting was associated with low dietary energy and fat intakes. In addition, trends towards lower preference for chocolate as well as for the taste of high-fat, low-sugar mixture were observed in those with higher leptin concentration. CONCLUSION: High serum leptin concentration could be associated in obese women with lower dietary energy and fat intakes, and possibly with the lower preference for fat. These findings need to be verified in further human studies.
Adult↗
Leptin concentrations are associated with higher proinsulin and insulin concentrations but a lower proinsulin/insulin ratio in non-diabetic subjects.
INTRODUCTION: Leptin (the product of the human OB gene) is increased in obese individuals, suggesting resistance to its effect. However, there is considerable variability in leptin levels at each level of body mass index (BMI), suggesting that genetic and environmental factors may regulate leptin concentrations. Previous data have suggested that leptin levels are associated with insulin resistance and in a few reports with impaired insulin secretion. We examined whether non-diabetic subjects, with elevated specific insulin and proinsulin levels, had increased leptin levels. METHODS: We used a radioimmunoassay (RIA) to measure serum leptin levels in 197 non-diabetic Mexican Americans and non-Hispanic whites from the San Antonio Heart Study. We also evaluated whether leptin levels were associated with impaired insulin secretion or increased beta cell stress, as evaluated by the fasting proinsulin/insulin ratio. (Higher fasting proinsulin/insulin ratios are thought to reflect impaired insulin secretion.) RESULTS: Leptin levels were significantly correlated with fasting specific insulin (r=0.55, P<0.001) and proinsulin (r=0.57, P<0.001) and inversely with the proinsulin/insulin ratio (r= -0.154, P=0.035) after adjustment for age, gender, ethnicity and 2 h glucose. These associations were similar in men and women and in Mexican Americans and in non-Hispanic whites. After further adjustment for BMI and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with specific insulin (r=0.31, P<0.001) and proinsulin (r=0.24, P<0.001) although the magnitude of the associations were considerably attenuated. CONCLUSION: We conclude that specific insulin and proinsulin are positively related to leptin levels and that these associations are to some degree independent of obesity and body fat distribution. Thus, subjects with increased insulin levels may be relatively resistant to the effects of leptin. However, leptin levels are associated with a decrease in the fasting proinsulin/insulin ratio suggesting that leptin levels are not associated with an impairment in insulin secretion.
Blood Glucose↗
Usual consumption of plant foods containing phytoestrogens and sex hormone levels in postmenopausal women in Wisconsin.
Consumption of phytoestrogens may reduce hormone-dependent cancer risk through alterations in the actions or metabolism of steroid hormones. Studies in humans of phytoestrogen-hormone interactions have been limited and inconsistent. Relations between the consumption of phytoestrogen-containing foods and serum sex hormones and sex hormone-binding globulin were studied in a population-based sample of postmenopausal women who participated in the Nutritional Factors in Eye Disease Study of the Beaver Dam Eye Study. Information on phytoestrogen-containing foods (broccoli, carrots, cauliflower, chili, dark bread, peas, and dried beans) was collected by interviewer-administered food-frequency questionnaires. Estrone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, and total and free testosterone were measured. Analyses included 246 postmenopausal women not taking hormone replacements. Partial correlations between hormones and intake of phytoestrogen-containing foods were computed, with adjustment for age, body mass index, years since menopause, and total energy intake. Number of standard servings per week of whole-grain products from the dark bread group was inversely associated with total testosterone (r = -0.20, p = 0.002). Although not statistically significant, other hormones displayed similar inverse associations with dark bread consistent with a common metabolic pathway. Although the magnitude of association was small, the data are consistent with the possibility that consumption of some phytoestrogen-containing foods may affect levels of testosterone in postmenopausal women.
Adult↗
Development of the multiple metabolic syndrome: an epidemiologic perspective.
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Cardiovascular Diseases↗
Insulin and 2-hour glucose levels are inversely related to Lp(a) concentrations controlled for LPA genotype.
In this study we assessed the relationship of lipoprotein(a) [Lp(a)] with diabetes status and with measures of glucose and insulin in a population of Mexican Americans having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Because of enormous allelic diversity at LPA [the locus encoding the apo(a) protein] that directly influences Lp(a) concentrations, it was first necessary to adjust for the large effects of variation at LPA. We calculated residual Lp(a) concentration as the difference between observed and expected; expected Lp(a) concentration was based on information from all family members sharing each identical-by-descent (IBD) allele. We found significant effects of sex and age on residual Lp(a) concentrations that increased with age (P=0.0004) and in females (P=0.0034). Although diabetes status per se was not related to residual Lp(a) concentrations (P=0.097), we found that residual Lp(a) concentrations were inversely correlated with fasting insulin (P=0.0017) and with insulin (P=0.0028) and glucose (P=0.0429) concentrations measured 2 hours after a glucose challenge. Furthermore, significant inverse correlations with the 2 insulin measures were observed for a subgroup of nondiabetic individuals. Inclusion of 2 lipid measures (plasma concentrations of cholesterol and triglycerides) in the models showed that the correlations with insulin and glucose were independent of the relationship between Lp(a) concentrations and the lipid measures. Also, we determined the residual size for each apo(a) isoform by adjusting for the IBD isoform group average. Although not related to diabetes status, residual apo(a) isoform size was positively correlated with fasting insulin (P=0.0013) and with 2-hour glucose (P=0.0246) and 2-hour insulin (P=0.0182) concentrations. In addition, significant correlations for all 4 measures were found for the subgroup of nondiabetic individuals. Thus, the results demonstrate that glucose-intolerant individuals have significantly lower residual Lp(a) concentrations and a significant increase of residual apo(a) size.
Alleles↗
Proinsulin and insulin concentrations in relation to carotid wall thickness: Insulin Resistance Atherosclerosis Study.
BACKGROUND AND PURPOSE: Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. METHODS: We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis. RESULTS: In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (r=0.087) and between ICA and proinsulin (r=0.101), split proinsulin (r = 0.092), and fasting insulin (r = 0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1). CONCLUSIONS: The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.
Arteriosclerosis↗
The importance of hyperglycemia in the nonfasting state to the development of cardiovascular disease.
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Acarbose↗
Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study.
Microalbuminuria is associated with excess cardiovascular mortality in both diabetic and nondiabetic subjects. Patients with NIDDM and microalbuminuria are more insulin resistant than those without microalbuminuria. However, the relationship between insulin resistance and microalbuminuria in patients with NIDDM could be due to hyperglycemia, which can cause both insulin resistance and an increase in albumin excretion rate. Little is known about microalbuminuria and insulin resistance in nondiabetic subjects. Therefore, we examined, cross-sectionally, the relationship of insulin sensitivity (S(I) x 10(-4) min x microU(-1) x ml(-1)), estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and fasting plasma insulin concentration, to microalbuminuria (albumin-to-creatinine ratio > or = 2 mg/mmol) in 982 nondiabetic subjects aged 40-69 years. Altogether, 15% of the subjects had microalbuminuria, and 32% had hypertension. Subjects with microalbuminuria had a lower degree of insulin sensitivity (means +/- SE, 1.70 +/- 0.11 vs. 2.25 +/- 0.07, P = 0.003) and higher fasting insulin concentrations (17.4 +/- 1.1 vs. 15.7 +/- 0.5 mU/l, P = 0.059) compared with subjects without microalbuminuria. In logistic regression analysis, an increasing degree of insulin sensitivity was related to a decreasing prevalence of microalbuminuria (odds ratio = 0.86, 95% CI: 0.79-0.94, P < 0.001). Although this relationship attenuated after adjustment for age, sex, ethnicity, hypertension, fasting glucose, and BMI, it still remained significant. The association between insulin sensitivity and microalbuminuria was shown not to be different between normotensive and hypertensive subjects. Our results suggest a relationship between insulin resistance and microalbuminuria in nondiabetic subjects that is partially dependent on blood pressure, glucose levels, and obesity.
Adult↗
Management of dyslipidemia in adults with diabetes.
Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
Adult↗
Impact of diabetes on mortality after the first myocardial infarction. The FINMONICA Myocardial Infarction Register Study Group.
OBJECTIVE: To study diabetic and nondiabetic patients with their first myocardial infarction to determine overall 1-year mortality, out-of-hospital mortality, 28-day mortality of hospitalized patients, and 1-year mortality of 28-day survivors. RESEARCH DESIGN AND METHODS: This study--based on the FINMONICA Myocardial Infarction Register, a part of the Finnish contribution to the WHO MONICA Project (World Health Organization Multinational Monitoring of Trends and Determinants of Cardiovascular Disease)--covered coronary heart disease (CHD) deaths and acute CHD events occurring during hospitalization among residents of Finland aged 25-64 years in three geographically defined areas. The study population comprised 620 diabetic and 3,445 nondiabetic patients who had their first myocardial infarction during the years 1988-1992. RESULTS: The age- and area-adjusted mortality rates and hazard ratios (HRs) for diabetic versus nondiabetic patients (95% CI) were as follows: The 1-year mortality rate was 44.2% in diabetic men and 32.6% in nondiabetic men (HR, 1.38; 1.18-1.61) and 36.9% in diabetic women and 20.2% in nondiabetic women (HR, 1.86; 1.40-2.46); the out-of-hospital mortality rate was 28.3% in diabetic men and 22.4% in nondiabetic men (HR, 1.25; 1.03-1.52) and 10.4% in diabetic women and 11.0% in nondiabetic women (HR, 0.95; 0.58-1.54); the 28-day mortality rate of hospitalized patients was 14.4% in diabetic men and 8.8% in nondiabetic men (HR, 1.58; 1.15-2.18) and 21.7% in diabetic women and 7.8% in nondiabetic women (HR, 2.60; 1.71-3.95); and the 1-year mortality rate of 28-day survivors was 9.6% in diabetic men and 5.0% in nondiabetic men (HR, 1.97; 1.25-3.12) and 10.7% in diabetic women and 2.5% in nondiabetic women (HR, 4.17; 2.05-8.51). CONCLUSIONS: The high mortality rate of diabetic patients after their first myocardial infarction and the high proportion of out-of-hospital deaths in this group imply that vigorous primary and secondary preventive measures should become an integral part of their medical care.
Adult↗
Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes.
OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.
Adult↗
Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study.
OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.
Adult↗
Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients.
OBJECTIVE: To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations. RESULTS: Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent. CONCLUSIONS: Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients.
1-Deoxynojirimycin↗