Showing papers in "Diabetes Care in 1996"
TL;DR: The suggestion that the different susceptibility of diabetic patients to microvascular and macrovascular complications may be a function of the endogenous antioxidant status is suggested.
Abstract: Long-term vascular complications still represent the main cause of morbidity and mortality in diabetic patients. Although prospective randomized long-term clinical studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between diabetic hyperglycemia and the development of secondary complications of diabetes, they have not defined the mechanism through which excess glucose results in tissue damage. Evidence has accumulated indicating that the generation of reactive oxygen species (oxidative stress) may play an important role in the etiology of diabetic complications. This hypothesis is supported by evidence that many biochemical pathways strictly associated with hyperglycemia (glucose autoxidation, polyol pathway, prostanoid synthesis, protein glycation) can increase the production of free radicals. Furthermore, exposure of endothelial cells to high glucose leads to augmented production of superoxide anion, which may quench nitric oxide, a potent endothelium-derived vasodilator that participates in the general homeostasis of the vasculature. In further support of the consequential injurious role of oxidative stress, many of the adverse effects of high glucose on endothelial functions, such as reduced endothelial-dependent relaxation and delayed cell replication, are reversed by antioxidants. A rational extension of this proposed role for oxidative stress is the suggestion that the different susceptibility of diabetic patients to microvascular and macrovascular complications may be a function of the endogenous antioxidant status.
1,966 citations
TL;DR: Major depressive disorder signals increased risk for onset of type II diabetes, and control variables were introduced for the use of health services, suggesting the treatment for depression led to an earlier diagnosis of diabetes in this sample.
Abstract: OBJECTIVE To determine whether depression is associated with an increased risk for onset of diabetes. RESEARCH DESIGN AND METHODS In 1981, a total of 3,481 household-residing adults participated in the Epidemiologic Catchment Area (ECA) Program survey at the East Baltimore site. A follow-up of that cohort after 13 years completed 1,897 interviews, amounting to >72% of survivors. In 1981, depression was assessed with the National Institutes of Mental Health (NIMH) Diagnostic Interview Schedule and diabetes, by self-report. This prospective analysis focused on subjects at risk for onset of diabetes by removing from the analysis individuals with diabetes in 1981. RESULTS There were 89 new cases of diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence of diabetes of 5.2%. In logistic models, major depressive disorder, but not milder forms of depression or other forms of psychiatric disorder, predicted the onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90–5.55). Controlling for age, race, sex, socioeconomic status, education, use of health services, other psychiatric disorders, and body weight did not weaken the relationship. CONCLUSIONS Major depressive disorder signals increased risk for onset of type II diabetes. Limitations of the findings arise from the difficulty in determining temporal order with two chronic conditions, even when the temporal order of measurement is clear. In addition, even though control variables were introduced for the use of health services, it is possible that the treatment for depression led to an earlier diagnosis of diabetes in this sample.
635 citations
TL;DR: It is concluded that the HOMA provides a useful model to assess ²-cell function in epidemiological studies and that it is important to take into account the degree of IR in assessing insulin secretion.
Abstract: OBJECTIVE Both insulin resistance (IR) and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess IR and secretion from the fasting glucose and insulin concentrations. RESEARCH DESIGN AND METHODS We applied the HOMA model in the 3.5-year follow-up of the Mexico City Diabetes Study. RESULTS Out of 1,449 subjects, 97 developed diabetes. When modeled separately insulin resistance but not insulin secretion predicted NIDDM. However, when both variables were entered into the same regression model, both increased IR and decreased β-cell function significantly predicted NIDDM. CONCLUSIONS We conclude that the HOMA provides a useful model to assess ²-cell function in epidemiological studies and that it is important to take into account the degree of IR in assessing insulin secretion.
568 citations
TL;DR: Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers and the recurrence data may indicate an improved quality of wound healing.
Abstract: OBJECTIVE To assess the effect of a tissue-engineered human dermis (Dermagraft) in healing diabetic foot ulcers. RESEARCH DESIGN AND METHODS This controlled prospective multicenter randomized single-blinded pilot study evaluated healing over a 12-week period in 50 patients with diabetic foot ulcers. These patients were randomized into four groups (three different dosage regimens of Dermagraft and one control group). All patients received identical care except for the use of Dermagraft tissue. Ulcer healing was assessed by percentage of wounds achieving complete or 50% closure, time to complete or 50% closure, and volume and area measurements. RESULTS Ulcers treated with the highest dosage of Dermagraft, one piece applied weekly for 8 weeks (group A), healed significantly more often than those treated with conventional wound closure methods; 50% (6 of 12) of the Dermagraft-treated and 8% (1 of 13) of the control ulcers healed completely ( P = 0.03). The percentage of wounds achieving 50% closure was also significantly higher (75 vs. 23%; P = 0.018), and the time to complete or 50% closure was faster ( P = 0.056). The group A regimen was more effective than other treatment regimens. All three were better than the control, however, and a dose-response was observed. There were no safety concerns. After a mean of 14 months of follow-up (range 11-22 months), there were no recurrences in the Dermagraft-healed ulcers. CONCLUSIONS Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers. The recurrence data may indicate an improved quality of wound healing.
387 citations
TL;DR: CSII therapy was associated with a marked and sustained reduction in the rate of severe hypoglycemia without adversely affecting the level of glycemic control attained during MDI therapy.
Abstract: OBJECTIVE To compare the incidence of severe hypoglycemia in patients crossed over from multiple daily injections (MDIs) of insulin to continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS From a population of 255 patients using CSII, all patients who met the following selection criteria were included in the present study: 1) a minimum of 12 months on intensive therapy with MDIs before switching to CSII, and 2) a minimum of 12 months on CSII after crossover. Glycemic control and adverse event rates for the 1-year MDI control period were compared with those for the CSII therapy period. RESULTS The incidence of severe hypoglycemia during MDI therapy declined from 138 to 22 events per 100 patient-years during the 1st year of CSII ( P 1c levels did not change significantly between the MDI phase and any year on CSII. However, in the subgroup of patients who had pre-CSII HbA 1c levels of ≥8.0%, the change to CSII was associated with a significant reduction in HbA 1c from baseline to year 1 (8.9 ± 0.8 vs. 8.1 ± 1.0%, P = 0.0004). The difference in diabetic ketoacidosis rates between the MDI year (14.6 events per 100 patientyears) and the CSII period (7.2 events per 100 patient-years) was not statistically significant. CONCLUSIONS CSII therapy was associated with a marked and sustained reduction in the rate of severe hypoglycemia without adversely affecting the level of glycemic control attained during MDI therapy. The more reproducible and flexible insulin delivery afforded by CSII was considered to be the major factor contributing to the improvement in severe hypoglycemia rates.
367 citations
TL;DR: Exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations, however, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients.
Abstract: OBJECTIVE Glucagon-like peptide I(7–36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients. It is not known whether GLP-1 has effects also in fasting type I diabetic patients. RESEARCH DESIGN AND METHODS In 11 type I diabetic patients (HbA 1c 9.1 ± 2.1%; normal, 4.2–6.3%), fasting hyperglycemia was provoked by halving their usual evening NPH insulin dose. In random order on two occasions, 1.2 pmol · kg −1 · min −1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 ± 0.9 mmol/l; plasma insulin 26 ± 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified fatty acids (enzymatic tests) were measured. RESULTS Glucagon was reduced from ∼8 to 4 pmol/l, and plasma glucose was lowered from 13.4 ± 1.0 to 10.0 ± 1.2 mmol/l with GLP-1 administration (plasma concentrations ∼100 pmol, P P P = 0.34), triglycerides ( P = 0.57), cholesterol ( P = 0.64), cortisol ( P = 0.40), or growth hormone ( P = 0.53). CONCLUSIONS Therefore, exogenous GLP-1 is able to lower fasting glycemia also in type I diabetic patients, mainly by reducing glucagon concentrations. However, this alone is not sufficient to normalize fasting plasma glucose concentrations, as was previously observed in type II diabetic patients, in whom insulin secretion (C-peptide response) was stimulated 20-fold.
363 citations
TL;DR: In this paper, the authors evaluated the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer.
Abstract: OBJECTIVE To evaluate the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer. RESEARCH DESIGN AND METHODS From August 1993 to August 1995, 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers. All the subjects underwent our diagnostic-therapeutic protocol and were randomized to undergo s-HBOT. Two subjects, one in the arm of the treated group and one in the arm of nontreated group, did not complete the protocol and were therefore excluded from the analysis of the results. Finally, 35 subjects received s-HBOT and another 33 did not. RESULTS Of the treated group (mean session = 38.8 ± 8), three subjects (8.6%) underwent major amputation: two below the knee and one above the knee. In the nontreated group, 11 subjects (33.3%) underwent major amputation: 7 below the knee and 4 above the knee. The difference is statistically significant ( P = 0.016). The relative risk for the treated group was 0.26 (95% CI 0.08–0.84). The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy: 14.0 ± 11.8 mmHg in treated group, 5.0 ± 5.4 mmHg in nontreated group ( P = 0.0002). Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT (odds ratio 0.084, P = 0.033, 95% CI 0.008–0.821) and indicated as negative prognostic determinants low ankle-brachial index values (odds ratio 1.715, P = 0.013, 95% CI 1.121–2.626) and high Wagner grade (odds ratio 11.199, P = 0.022, 95% CI 1.406–89.146). CONCLUSIONS s-HBOT, in conjunction with an aggressive multidisciplinary therapeutic protocol, is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers.
361 citations
TL;DR: It appears that the high TG–low HDL cholesterol dyslipidemia frequently found in visceral obesity and in a hyperinsulinemic state is a strong correlate of the small dense LDL phenotype.
Abstract: OBJECTIVE To investigate the potential relationship between the cluster of metabolic abnormalities found in visceral obesity and the small dense LDL phenotype RESEARCH DESIGN AND METHODS We have estimated LDL peak particle size by nondenaturing 2–16% gradient gel electrophoresis in a sample of 79 men Glucose tolerance and fasting plasma insulin and lipoprotein levels were also measured RESULTS The LDL particle score, calculated from migration, distances and relative band intensities and reflecting the proportion of small dense LDL particles, was positively correlated with plasma triglyceride (TG) ( r = 060, P r = −056, P r = 060, P r = 023 and 029, respectively, P CONCLUSIONS It thus appears that the high TG–low HDL cholesterol dyslipidemia frequently found in visceral obesity and in a hyperinsulinemic state is a strong correlate of the small dense LDL phenotype Although associated with the dense LDL phenotype, visceral obesity and hyperinsulinemia were not independent predictors of an increased proportion of small dense LDL particles after controlling for TG and HDL cholesterol levels
337 citations
TL;DR: The purpose of this technical review is to provide the detailed background to the American Diabetes Association's Position Statement on clinical guidelines for pre-conception care of women with diabetes.
Abstract: As noted by many previous reviewers (1-4), major congenital malformations remain the leading cause of mortality and serious morbidity in infants of mothers with established diabetes (IDM). In addition to the associated human suffering, the malformations are very expensive in both shortand long-term health care costs. The purpose of this technical review is to provide the detailed background to the American Diabetes Association's Position Statement on clinical guidelines for pre-conception care of women with diabetes (5-7a). The review is organized to discuss several related topics.
304 citations
TL;DR: The findings indicate caution about encouragement of maximal self-care autonomy among youth with IDDM and suggest that families who succeed in maintaining parental involvement in diabetes management may have better outcomes.
Abstract: OBJECTIVE Treatment of IDDM in youth emphasized balancing children9s self-care autonomy with their psychological maturity. However, few data exist to guide clinicians or parents, and little is known about correlates of deviations from this ideal. RESEARCH DESIGN AND METHODS In this cross-sectional study, IDDM self-care autonomy of 100 youth was assessed using two well-validated measures. Three measures of psychological maturity (cognitive function, social-cognitive development, and academic achievement) were also collected for each child. Composite indexes of self-care autonomy and of psychological maturity were formed, and the ratio of the self-care autonomy index to the psychological maturity index quantified each child9s deviation from developmentally appropriate IDDM self-care autonomy. Based on these scores, participants were categorized as exhibiting constrained (lower tertile), appropriate (middle tertile), or excessive (higher tertile) self-care autonomy. Between-group differences in treatment adherence, diabetes knowledge, glycemic control, and hospitalization rates were explored. RESULTS Analysis of covariance controlling for age revealed that the excessive self-care autonomy group demonstrated less favorable treatment adherence, diabetes knowledge, hospitalization rates, and, marginally, glycemic control. Excessive self-care autonomy increased with age and was less common among intact two-parent families but was unrelated to other demographic factors. CONCLUSIONS The findings indicate caution about encouragement of maximal self-care autonomy among youth with IDDM and suggest that families who succeed in maintaining parental involvement in diabetes management may have better outcomes.
288 citations
TL;DR: Glucose effectiveness is a component equal to or greater than insulin itself in the determination of glucose tolerance and appears to be the insulinopenic state, although this hypothesis requires further validation.
Abstract: I nsulin secretion and insulin action are major factors in the determination of glucose tolerance, and insulinopenia and insulin resistance cause glucose intolerance and/or NIDDM. Because glucose itself can enhance glucose disposal and suppress endogenous glucose production independent of a change in insulin, it is necessary to consider an additional factor in determination of glucose tolerance: glucose effectiveness. This phenomenon represents the ability of glucose per se, under basal insulin conditions, to enhance glucose disposal and to suppress endogenous glucose production. Glucose effectiveness has been measured in many studies in which glucose disposal and output have been quantified at basal insulin but with widely varying glycemia. The effect of glucose on glucose disposal in humans is such that a 100 mg/dl increase in plasma glucose (at basal insulin) will increase glucose disposal by 1.63 mg • min ' -kg '. Similarly, the same 100 mg/dl increment in glucose alone will suppress endogenous glucose output by 0.79 mg • min ' • kg '. Thus, two-thirds of glucose effectiveness in humans is the disposal effect [1.63/(1.63 + 0.79)] and the remaining third is the effect to suppress the liver. Having numerical values for glucose effectiveness makes it possible to calculate the importance of hyperglycemia per se relative to the importance of insulin to disposition of a glucose load. In normal individuals, ~50% of the glucose disposal during an oral glucose tolerance test (OGTT) is due to glucose effectiveness and not to the dynamic insulin response. In the insulin-resistant obese individual, 83% of glucose disposal occurs independent of the dynamic insulin response; in NIDDM, because of severe insulin resistance and relative insulinopenia, 99% of glucose uptake after a carbohydrate meal is due to glucose effectiveness. Thus, glucose effectiveness is a component equal to or greater than insulin itself in the determination of glucose tolerance. Glucose effectiveness can be assessed from the intravenous glucose tolerance test (IVGTT) by using the so-called minimal model approach; the sensitivity parameter that is calculated, the glucose effectiveness index (5G) represents the sum, or whole-body, effect of hyperglycemia to enhance glucose disposal and to suppress endogenous glucose production. Using the model, SG has been measured multiple times in humans: the average from 18 independent studies is 0.024 min". Physical activity and training almost double SG; states of glucose intolerance are characterized by reduced SG. For example, SG is down 33% in offspring of two parents with NIDDM, down by 50% in subjects with impaired glucose tolerance, and reduced as much as 60% in subjects on a very-low-calorie diet. A hallmark of states of reduced SG appears to be the insulinopenic state, although this hypothesis requires further validation. Whether reduced glucose effectiveness is a true inheritable defect that can enhance risk for and contribute to the onset of NIDDM remains to be investigated. Recent evidence that glucose can
TL;DR: A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs, suggesting that HCV may have a direct role in the development of diabetes.
Abstract: OBJECTIVE To evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. RESEARCH DESIGN AND METHODS A total of 176 consecutive diabetic patients were compared with 6,172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided in two groups according to their HCV antibody status and analyzed for the following variables: age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusions, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests (LFTs). RESULTS A higher prevalence of HCV infection was observed in diabetic patients in comparison with blood donors (11.5 vs. 2.5%; P P CONCLUSIONS A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic patients with an abnormal LFT is mandatory. The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes.
TL;DR: A model of the determinants of adherence to diabetes self-care that incorporates the effects of patient participation in medical decision making is introduced and suggested three ways that patient participation can affect adherence to self- care are suggested.
Abstract: For patients, treatment of diabetes involves complex changes in basic behaviors and adherence to complicated regimens. Understanding the factors that enable patients to adhere to diabetes treatment is the first step to designing effective interventions. Researchers of diabetes care have postulated that increasing diabetic patients' participation in medical decision making during the doctor visit is likely to improve their adherence to self-care. However, a critical review of the impact of patient participation on diabetic patients adherence to self-care is absent from the literature. We review the subject of patient participation in medical decision making and its effect on adherence to self-care for patients with diabetes. We introduce a model of the determinants of adherence to diabetes self-care that incorporates the effects of patient participation in medical decision making. In this model, we suggest three ways that patient participation can affect adherence to self-care: 1) it may have a direct effect; 2) it may affect adherence to self-care indirectly by affecting patients' understanding of their treatment regimen or the fit of their regimen with their lifestyle; and 3) perceived omissions of participation can affect adherence to self-care indirectly through an effect on patient satisfaction. Research is needed to identify more clearly which components of patient participation affect adherence to self-care and in what ways. Distinguishing patient and physician behaviors that contribute to the process of patient participation would provide a means to develop specific behavioral interventions.
TL;DR: It is suggested that better glycemic control in type II diabetes is associated with fewer physical symptoms, better mood, and better well-being, in a nonhypoglycemic HbA1c range.
Abstract: OBJECTIVE To describe the cross-sectional relation between glycemic control and physical symptoms, emotional well-being, and general well-being in patients with type II diabetes. RESEARCH DESIGN AND METHODS The study population consisted of 188 patients with type II diabetes between 40 and 75 years of age. Patients were treated with blood glucose-lowering agents or had either a fasting venous plasma glucose level ≥7.8 mmol/l or an HbA 1c level > 6.1%. Multiple regression analyses were performed. Dependent variables were scores on the Type II Diabetes Symptom Checklist, the Profile of Mood States, the Affect Balance Scale, and questions regarding general well-being. The primary determinant under study was HbA 1c . In addition, age, sex, neuroticism (indicating a general tendency to complain), insulin use, and comorbidity were included as determinants in all analyses. Other potential determinants taken into consideration were hypoglycemic complaints, marital status, diabetes duration, cardiovascular history, blood pressure, BMI, waist-to-hip ratio, perceived burden of treatment, and smoking. None of these potential determinants had to be included to correct confounding of the relation between HbA 1c and well-being scores. RESULTS Higher HbA 1c levels were significantly associated with higher symptom scores (total score, hyperglycemic score, and neuropathic score), with worse mood (total score, displeasure score, depression, tension, fatigue), and with worse general well-being. The relative risks varied between 1.02 and 1.36 for each percentage difference in HbA 1c . The relation between HbA 1c and some mood states was modified by neuroticism: in the less neurotic patient (i.e., one who is less inclined to complain), the relation was more evident. CONCLUSIONS These data suggest that better glycemic control in type II diabetes is associated with fewer physical symptoms, better mood, and better well-being, in a nonhypoglycemic HbA 1c range.
TL;DR: A significant excess incidence of both diabetes- and non-diabetes-related amputations and proportionally more proximal amputations were identified in African-Americans compared with Hispanics andNon-Hispanic whites.
Abstract: OBJECTIVE To identify the age-adjusted and level-specific incidence of amputations associated with diabetes in Hispanics, African-Americans, and non-Hispanic whites. RESEARCH DESIGN AND METHODS We used a database from the Office of Statewide Planning and Development in California that identified all hospitalizations for lower-extremity amputations in the state in 1991. Amputation level was defined by ICD-9-CM codes 84.11–84.18 and were categorized as toe, foot, leg, and thigh amputations. RESULTS The age-adjusted incidence of diabetes-related amputation per 10,000 persons with diabetes in 1991 was 95.25 in African-Americans, 55.98 in non-Hispanic whites, and 44.43 in Hispanics. Hispanics had a higher proportion of amputations (82.7%) associated with diabetes than did African-Americans (61.6%) or non-Hispanic whites (56.8%) ( P P CONCLUSIONS Hispanics had proportionally more amputations associated with diabetes than did African-Americans or non-Hispanic whites. A significant excess incidence of both diabetes- and non-diabetes-related amputations and proportionally more proximal amputations were identified in African-Americans compared with Hispanics and non-Hispanic whites. A possible explanation could be the higher prevalence of peripheral vascular disease in African-Americans. Public health initiatives, which have been demonstrated to reduce the incidence of diabetes-related lower-extremity amputations, should be implemented, and additional work should focus on minority groups.
TL;DR: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.
Abstract: OBJECTIVE The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.
TL;DR: The 50% decrease in glycemic response that was observed after the ingestion of 35 g carbohydrate is estimated to occur with ∼5 g β-glucan, which can easily be attained without the loss of taste by incorporating oat bran concentrate in products.
Abstract: OBJECTIVE To determine whether increasing doses (amounts) of β-glucan present in an extruded breakfast cereal affect the glycemic and insulinemic responses in eight NIDDM subjects, compared with the same responses after a continental breakfast (bread, milk, cheese, ham). RESEARCH DESIGN AND METHODS Breakfast cereals were produced using various proportions of oat bran enriched in fiber, which contain an unusually high amount of a viscous polysaccharide, called β-glucan, and oat bran. The carbohydrate load was 35 g. RESULTS The maximum increases observed in plasma glucose after the breakfast cereal were 67% ( P P P 2 = 0.94, P P CONCLUSIONS The 50% decrease in glycemic response that was observed after the ingestion of 35 g carbohydrate is estimated to occur with ∼5 g β-glucan. This dose of β-glucan can easily be attained without the loss of taste by incorporating oat bran concentrate in products.
TL;DR: It is concluded that insulin suppresses VLDL production in insulin-sensitive humans partly by suppressing plasma FFA levels and partly by a non-FFA-mediated (perhaps direct hepatic) mechanism.
Abstract: The role of hyperinsulinemia in the pathogenesis of triglyceride (TG) and VLDL over-production in insulin-resistant states remains controversial. While studies in humans and animals have generally suggested that chronic hyperinsulinemia facilitates VLDL production, particularly in the presence of an abundant supply of substrate for VLDL synthesis, the majority of in vitro studies using cultured hepatocytes and hepatoma cell lines have demonstrated an acute inhibitory effect of insulin. Using radiolabeled VLDL tracers we have examined the acute effect of hyperinsulinemia on VLDL production in humans. We found a rapid suppression of plasma free fatty acid (FFA) levels in response to insulin and a consistent 50-60% insulin-induced suppression of both VLDL TG and VLDL apolipoprotein (apo) B in lean insulin-sensitive individuals. Elevation of plasma FFA levels by infusing heparin and Intralipid without hyperinsulinemia resulted in a marked increase in VLDL TG and VLDL apoB production. When the insulin-induced suppression of plasma FFA levels was prevented during hyperinsulinemia, VLDL TG production was still inhibited, although to a lesser extent than with insulin alone. We concluded from these findings that insulin suppresses VLDL production in insulin-sensitive humans partly by suppressing plasma FFA levels and partly by a non-FFA-mediated (perhaps direct hepatic) mechanism. In addition, we found that chronically insulin-resistant hyperinsulinemic obese individuals were resistant to this suppressive effect of insulin on VLDL apoB production, in keeping with similar findings by others performing in vitro experiments using cultured hepatocytes isolated from insulin-resistant or hyperinsulinemic rats. The relevance of these findings to the mechanism of hypertriglyceridemia associated with chronic insulin-resistant states in humans remains a matter of speculation. One hypothesis is that resistance to the normal suppressive effect of insulin, in association with other metabolic abnormalities associated with insulin resistance, may contribute to postprandial and postabsorptive hypertriglyceridemia.
TL;DR: In spite of the frequency of PCP visits during the year for many of these patients, diabetes management was inadequate, creating an increased risk of the development of the acute and chronic complications of diabetes, and an even greater future burden on the health care system and negative consequences for patients.
Abstract: OBJECTIVE To document the quality of diabetes care provided to patients in a large health maintenance organization (HMO) from 1 January 1993 to 1 January 1994 and compare it to the standards of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS To meet a Health Plan and Employer Data Information Set (HEDIS) requirement, a major HMO in California identified 14,539 members with diabetes and randomly selected 384 individuals for review. Charts were available on 353 of these patients, and after obtaining the information for the HEDIS review, additional information was extracted from the charts by an outside chart reviewer. This data set was used for an analysis of the quality of diabetic care provided by the participating medical groups to these HMO members during 1 year. Documentation of follow-up and measures of glycemic and lipid control was examined both for absolute values and for the frequency of measurement over the year. These results were compared to the ADA standards of care. RESULTS Although patients averaged 4.5 visits to their primary care physicians (PCPs) over the year, 21% had one or fewer visits per year. Glycated hemoglobin levels were not documented in 56% of patients (ADA recommends two to four measurements per year), and of those with a glycated hemoglobin level measured. 39% had at least one value ≥ 10%. Fasting plasma glucose concentrations were not documented in 65% of patients (four to six per year recommended). Foot exams (which should be performed at each regular visit) were not documented for 94% of patients. Urine protein measurements were not performed in 52% of patients. Additionally, many patients had elevated and untreated lipid abnormalities. CONCLUSIONS In spite of the frequency of PCP visits during the year for many of these patients, diabetes management was inadequate. This lack of adequate preventive care will lead to an increased risk of the development of the acute and chronic complications of diabetes, creating an even greater future burden on the health care system and negative consequences for patients.
TL;DR: A term is proposed, "visceral fat syndrome," as a highly atherogenic state, which includes visceral fat accumulation, glucose intolerance, hyperlipidemia, and hypertension, which is proposed to be more remarkable in VFO than in SFO.
Abstract: Body fat distribution can be assessed by computed tomography (CT). The ratio of umbilicus was used to classify obese subjects as having visceral fat obesity (VFO) or subcutaneous fat obesity (SFO). Serum triglyceride and total cholesterol levels and plasma glucose area in an oral glucose tolerance test were higher in patients with VFO than in those with SFO. Significant positive correlations were demonstrated between V/S ratio and plasma glucose area, serum triglyceride level, and total cholesterol level as well as systolic or diastolic blood pressure. VFO was more frequently associated with coronary artery disease. Moreover, VFO was more often accompanied by multiple risk factors than was SFO. Steady-state plasma glucose (SSPG) level was significantly higher in patients with VFO than with SFO, suggesting that insulin resistance may be more remarkable in VFO than in SFO. Furthermore, visceral fat accumulation was also associated with these complications even in nonobese subjects. Visceral fat area (VFA) was significantly correlated with fasting plasma glucose, serum triglyceride, and total cholesterol levels. Animal models such as Goto-Kakizaki (GK) rats with ventromedial hypothalamus (VMH) lesions and Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were accompanied by visceral fat accumulation and an early stage of aortic atherosclerosis. Aging, sex hormone, genetic, and dietary factors and physical inactivity may induce visceral fat accumulation. Visceral fat is characterized by its high lipogenic activity as well as its accelerated lipolytic activity. High levels of portal free fatty acids (FFAs) may eventually result in an enhancement of hepatic triglyceride synthesis, causing hyperlipidemia. High portal FFA levels would also induce insulin resistance, thereby causing glucose intolerance, hypertension, and finally atherosclerosis. We propose a term, "visceral fat syndrome," as a highly atherogenic state, which includes visceral fat accumulation, glucose intolerance (insulin resistance), hyperlipidemia, and hypertension.
TL;DR: Erectile dysfunction was associated with presence of severe diabetic retinopathy, a history of peripheral neuropathy, amputation, cardiovascular disease, a higher glycosylated hemoglobin, use of antihypertensive medications, and higher BMI.
Abstract: OBJECTIVE The purpose of this report is to examine the prevalence of erectile dysfunction and relationships to other characteristics in men with younger-onset diabetes. RESEARCH DESIGN AND METHODS In a population-based cohort study in southern Wisconsin, prevalence of erectile dysfunction was measured based on self reports in men who were 21 years of age or older, were n = 365). RESULTS Of the study group, 20% reported a history of erectile dysfunction. The prevalence of erectile dysfunction increased with increasing age (from 1.1% in those 21–30 years of age to 47.1% in those 43 years of age or older, P for trend P for trend CONCLUSIONS These data suggest that tighter glycemic control and careful selection of antihypertensive medications might prove beneficial.
TL;DR: The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers.
Abstract: OBJECTIVE To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean ± SD duration of diabetes was 14.7 ± 9.3 years. RESULTS The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15–29 years old to 25% in patients 45–59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA 1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA 1c , prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.
TL;DR: DH Pressure Relief Walkers were as effective as total contact casts to reduce foot pressures at ulcer sites and may be an effective practical addition in the treatment of foot ulcers.
Abstract: OBJECTIVE To compare the effectiveness of total contact casts, commercially available therapeutic shoes, and removable walking casts to reduce mean peak plantar foot pressures at the site of neuropathic ulcerations in diabetic subjects. RESEARCH DESIGN AND METHODS We compared the reduction in peak plantar pressures at ulcer sites under the great toe ( n = 5), first metatarsal ( n = 10), and second through fifth metatarsals ( n = 10) using six treatments: total contact casts (TCCs), DH Pressure Relief Walkers (DH), Aircast Pneumatic Walkers, Three D Dura-Steppers (3D), CAM Walkers, and P.W. Minor Xtra Depth shoes. A rubber sole canvas oxford was used to establish baseline pressure values. The canvas oxford could be viewed as a worse-case scenario for this patient population. With the EMED Pedar in-shoe pressure measurement system, data for 40 steps were collected for each treatment. We used Tukey9s Studentized Range Test for simultaneous multiple comparisons to compare treatments. RESULTS DH Pressure Relief Walkers reduced plantar pressures significantly better than other commercially available treatments for ulcers under the first metatarsal, second through fifth metatarsals, and great toe ( P CONCLUSIONS DH Pressure Relief Walkers were as effective as total contact casts to reduce foot pressures at ulcer sites and may be an effective practical addition in the treatment of foot ulcers.
TL;DR: Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate support the pathogenetic role of cigarette smoking on cardiovascular risk factors.
Abstract: OBJECTIVE To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate. RESEARCH DESIGN AND METHODS This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min. RESULTS Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 ± 1.03 mmol/l (mean ± SE) (95% CI 22.9–28) during the smoking OGTT and 21.8 ± 0.85 mmol/l (CI 19.2–24.3) in the control OGTT ( P P P P CONCLUSIONS Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.
TL;DR: It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals and may be related to greater muscle glycogen utilization during exercise.
Abstract: OBJECTIVE The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. RESEARCH DESIGN AND METHODS Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and Vo 2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% Vo 2peak for 70 min or 70% Vo 2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. RESULTS The average caloric expenditure did not differ between exercise at 50 and 70% Vo 2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher ( P 2peak in obese subjects (77 ± 5 vs. 68 ± 6 g) and obese NIDDM subjects (70 ± 4 vs. 58 ± 6 g). Muscle glycogen utilization was also higher ( P 2peak in obese subjects (59 ± 9 vs. 30 ± 7 g) and in obese NIDDM subjects (48 ± 5 vs. 24 ± 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% Vo 2peak . Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% Vo 2peak . However, plasma insulin response area was reduced ( P 2peak (9,644 ± 1,783 vs. 7,538 ± 1,522 μ· ml "1 · 180 min "1 ). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% Vo 2peak . CONCLUSIONS It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% Vo 2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% Vo 2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.
TL;DR: Diabetic patients have a mortality rate during the 2-year period after CABG that is about twice that of nondiabetic patients during both the early and late phase after the operation.
Abstract: OBJECTIVE To describe mortality and morbidity during a 2-year period after coronary artery bypass grafting (CABG) among diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS All the patients in western Sweden in whom CABG was undertaken between June 1988 and June 1991 and in whom concomitant procedures were not performed were registered prospectively. The study was a prospective follow-up. RESULTS Diabetic patients ( n = 268) differed from nondiabetic patients ( n = 1,859) in that more women were included, and the patients more frequently had a previous history of myocardial infarction (MI), hypertension, congestive heart failure, intermittent claudication, and obesity. Diabetic patients more frequently required reoperation and had a higher incidence of peri- and postoperative neurological complications. Mortality during the 30 days after CABG was 6.7% in diabetic patients versus 3.0% in nondiabetic patients ( P P P CONCLUSIONS Diabetic patients have a mortality rate during the 2-year period after CABG that is about twice that of nondiabetic patients during both the early and late phase after the operation.
TL;DR: Hyperinsulinemia may be responsible for part of the observed association of both diabetes and obesity with BMD in women, and is speculated to be an osteogenic factor.
Abstract: OBJECTIVE Obesity and NIDDM are each associated with increased bone mineral density (BMD). We therefore hypothesize that hyperinsulinemia is an osteogenic factor. RESEARCH DESIGN AND METHODS Subjects consisted of 411 men and 559 women aged 50–89 years who were participants in the Rancho Bernardo Heart and Chronic Disease Study and were not diabetic by history or oral glucose tolerance test. Fasting and 2-h postchallenge insulin were measured by radioimmunoassay. Bone mineral density was measured at the midshaft radius with single photon absorptiometry and at the lumbar spine and hip with dual energy X-ray absorptiometry. RESULTS Multiple regression analyses indicated that among men, a significant insulin-BMD association at the hip was no longer apparent after adjusting for covariates. Among women, fasting insulin was significantly and positively associated with bone density of the radius and spine ( P 2 of the radius and spine, respectively. CONCLUSIONS Hyperinsulinemia may be responsible for part of the observed association of both diabetes and obesity with BMD in women.
TL;DR: Troglitazone at 400 mg/day decreased FPG and HbA1c significantly in NIDDM patients who had failed to respond to diet therapy, and can be a useful hypoglycemic agent for the treatment of NID DM.
Abstract: OBJECTIVE To investigate the clinical efficacy of troglitazone, a newly developed oral hypoglycemic agent, in patients with NIDDM. RESEARCH DESIGN AND METHODS There were 284 NIDDM patients (20–82 years of age) whose glycemic control while on a diet was judged stable but was judged unsatisfactory (fasting plasma glucose [FPG] ≥ 8.3 mmol/l) when entered into a multicenter and double-blind study with parallel groups study. They were randomly allocated into two groups, the troglitazone group (the T group: 400 mg/day p.o.) and the placebo group (the P group), and were treated with test drugs for 12 weeks. RESULTS We evaluated efficacy in 136 patients of the T group and 126 patients of the P group. There was no significant difference in any of baseline characteristics between the T and P groups. In the T group, FPG and HbA 1c decreased significantly after treatment (before versus after, FPG 10.1 ± 1.6 vs. 8.8 ± 1.9 mmol/l, P 1c : 8.6 ± 1.5 vs 8.1 ± 1.7%, P 1c did not change after treatment in the P group (before versus after, FPG 10.1 ± 1.8 vs. 9.9 ± 2.1 mmol/l; HbA 1c 8.5 ± 1.5 vs. 8.6 ± 1.6%). Of 136 patients in the T group, 62 (45.6%) were classified as responders. Serum triglyceride level also decreased in the T group but not in the P group. Body weight increased slightly only in the T group. There were no differences in changes in blood pressure between the two groups. No serious adverse events occurred in either group. CONCLUSIONS Troglitazone at 400 mg/day decreased FPG and HbA 1c significantly in NIDDM patients who had failed to respond to diet therapy. Troglitazone, developed as a drug to enhance insulin action, can be a useful hypoglycemic agent for the treatment of NIDDM.
TL;DR: Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.
Abstract: OBJECTIVE We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population.
RESEARCH DESIGN AND METHODS From all three hospitals in a city of ∼ 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes.
RESULTS Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000−1 · year−1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power.
CONCLUSIONS We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.
TL;DR: It is concluded that GHb is a better predictor of CVD and IHD mortality than FPG or PCPG in women without diabetes; no single measure of glycemia was predictive in men.
Abstract: OBJECTIVE To examine the relation between GHb, fasting plasma glucose (FPG), postchallenge plasma glucose (PCPG), and mortality from cardiovascular disease (CVD) and ischemic heart disease (IHD) in older adults. RESEARCH DESIGN AND METHODS A community-based study of 1,239 nondiabetic older adults followed for an average of 8 years, from baseline (1984–1987) to 1993. RESULTS GHb, but not FPG or PCPG, was significantly related to CVD and IHD mortality in women but not men. The age-adjusted relative hazard for those in the highest quintile of GHb (≥ 6.7%) compared with women with lower levels was 2.37 for fatal CVD (95% CI = 1.30−4.31, P = 0.005) and 2.43 for IHD (95% CI = 1.12−5.25, P = 0.024). This association persisted after adjustment for all covariates (age, systolic blood pressure, BMI, LDL, HDL, triglycerides, cigarette smoking, antihypertensive medication use, and estrogen use). GHb was significantly associated with LDL and HDL levels in women, but the association between GHb and CVD or IHD persisted after adjustment for these lipoproteins. CONCLUSIONS We concluded that GHb is a better predictor of CVD and IHD mortality than FPG or PCPG in women without diabetes; no single measure of glycemia was predictive in men. The reason for the sex difference is unexplained.