Showing papers in "Diabetes Care in 2004"
TL;DR: Findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant, and given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
Abstract: OBJECTIVE —The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030. RESEARCH DESIGN AND METHODS —Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations’ population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries. RESULTS —The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age. CONCLUSIONS —These findings indicate that the “diabetes epidemic” will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
16,648 citations
TL;DR: The HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data, however, as with all models, the primary input data needs to be robust, and the data need to be interpreted carefully.
Abstract: Homeostatic model assessment (HOMA) is a method for assessing beta-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than beta-cell function. This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in beta-cell function were modeled by changing the beta-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods. We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring beta-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose. In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.
4,360 citations
TL;DR: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population.
Abstract: OBJECTIVE —It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS —In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI ≥30 kg/m 2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS —Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients ( P P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P P CONCLUSIONS —Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT and or NGT.
1,706 citations
TL;DR: Increases in high blood pressure, waist circumference, and hypertriglyceridemia accounted for much of the increase in the prevalence of the metabolic syndrome, particularly among women.
Abstract: OBJECTIVE —The prevalence of the metabolic syndrome is high among U.S. adults. Our purpose was to determine whether the prevalence of this syndrome has changed since 1988–1994. RESEARCH DESIGN AND METHODS —A total of 6,436 men and women aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and 1,677 participants from NHANES 1999–2000 were included in the analyses. We used the definition of the metabolic syndrome developed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. RESULTS —The unadjusted prevalence of the metabolic syndrome was 23.1% in NHANES III and 26.7% in NHANES 1999–2000 ( P = 0.043), and the age-adjusted prevalences were 24.1 and 27.0% ( P = 0.088), respectively. The age-adjusted prevalence increased by 23.5% among women ( P = 0.021) and 2.2% among men ( P = 0.831). Increases in high blood pressure, waist circumference, and hypertriglyceridemia accounted for much of the increase in the prevalence of the metabolic syndrome, particularly among women. CONCLUSIONS —The increased prevalence of the metabolic syndrome is likely to lead to future increases in diabetes and cardiovascular disease.
1,514 citations
TL;DR: Exenatide significantly reduced HbA(1c) in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy and was associated with weight loss.
Abstract: OBJECTIVE —This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy RESEARCH DESIGN AND METHODS —This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the US After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 ± 11 years, BMI 33 ± 6 kg/m 2 , HbA 1c 86 ± 12% [±SD]) and began 4 weeks at 5 μg subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo Subsequently, subjects in arm B were escalated to 10 μg bid exenatide All subjects continued sulfonylurea therapy RESULTS —At week 30, HbA 1c changes from baseline were −086 ± 011, −046 ± 012, and 012 ± 009% (±SE) in the 10-μg, 5-μg, and placebo arms, respectively (adjusted P 1c > 7% ( n = 237), 41% (10 μg), 33% (5 μg), and 9% (placebo) achieved HbA 1c ≤ 7% ( P P P CONCLUSIONS —Exenatide significantly reduced HbA 1c in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea Exenatide was generally well tolerated and was associated with weight loss
1,345 citations
TL;DR: Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 1 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
Abstract: There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
1,341 citations
TL;DR: The ADA concluded that aripiprazole and ziprasidone have no effect on the risk of diabetes, solely based on data from clinical trials that did not include these two drugs in epidemiological studies.
Abstract: In the February 2004 issue of Diabetes Care , the American Diabetes Association (ADA) published a summary of their conclusions drawn from the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes (1). Although the ADA ranked the diabetes risk for second-generation antipsychotics (SGAs), the U.S. Food and Drug Administration’s Division of Neuropharmacological Drug Products (DNDP) does not believe that the evidence currently available allows such a ranking.
The ADA concluded that aripiprazole and ziprasidone have no effect on the risk of diabetes. The ADA notes that because these two drugs have not been included in epidemiological studies, this conclusion is solely based on data from clinical trials that did not …
1,232 citations
TL;DR: The purpose of this technical review is to evaluate the evidence relating to the management of hyperglycemia in hospitals, with particular focus on the issue of glycemic control and its possible impact on hospital outcomes.
Abstract: Diabetes increases the risk for disorders that predispose individuals to hospitalization, including coronary artery, cerebrovascular and peripheral vascular disease, nephropathy, infection, and lower-extremity amputations. The management of diabetes in the hospital is generally considered secondary in importance compared with the condition that prompted admission. Recent studies (1,2) have focused attention to the possibility that hyperglycemia in the hospital is not necessarily a benign condition and that aggressive treatment of diabetes and hyperglycemia results in reduced mortality and morbidity. The purpose of this technical review is to evaluate the evidence relating to the management of hyperglycemia in hospitals, with particular focus on the issue of glycemic control and its possible impact on hospital outcomes. The scope of this review encompasses adult nonpregnant patients who do not have diabetic ketoacidosis or hyperglycemic crises.
For the purposes of this review, the following terms are defined (adapted from the American Diabetes Association [ADA] Expert Committee on the Diagnosis and Classification of Diabetes Mellitus) (3):
The prevalence of diabetes in hospitalized adult patients is not known. In the year 2000, 12.4% of hospital discharges in the U.S. listed diabetes as a diagnosis. The average length of stay was 5.4 days (4). Diabetes was the principal diagnosis in only 8% of these hospitalizations. The accuracy of using hospital discharge diagnosis codes for identifying patients with …
1,193 citations
TL;DR: It is confirmed that many patients for whom diabetes medication was prescribed were poor compliers with treatment, including both OHAs and insulin, however, electronic monitoring systems were useful in improving adherence for individual patients.
Abstract: OBJECTIVE —The purpose of this study was to determine the extent to which patients omit doses of medications prescribed for diabetes. RESEARCH DESIGN AND METHODS —A literature search (1966–2003) was performed to identify reports with quantitative data on adherence with oral hypoglycemic agents (OHAs) and insulin and correlations between adherence rates and glycemic control. Adequate documentation of adherence was found in 15 retrospective studies of OHA prescription refill rates, 5 prospective electronic monitoring OHA studies, and 3 retrospective insulin studies. RESULTS —Retrospective analyses showed that adherence to OHA therapy ranged from 36 to 93% in patients remaining on treatment for 6–24 months. Prospective electronic monitoring studies documented that patients took 67–85% of OHA doses as prescribed. Electronic monitoring identified poor compliers for interventions that improved adherence (61–79%; P CONCLUSIONS —This review confirms that many patients for whom diabetes medication was prescribed were poor compliers with treatment, including both OHAs and insulin. However, electronic monitoring systems were useful in improving adherence for individual patients. Similar electronic monitoring systems for insulin administration could help healthcare providers determine patients needing additional support.
1,119 citations
TL;DR: In a primary care population, diabetes self-care was suboptimal across a continuum from home-based activities, such as healthy eating, exercise, and medication adherence, to use of preventive care.
Abstract: OBJECTIVE —We assessed whether diabetes self-care, medication adherence, and use of preventive services were associated with depressive illness.
RESEARCH DESIGN AND METHODS —In a large health maintenance organization, 4,463 patients with diabetes completed a questionnaire assessing self-care, diabetes monitoring, and depression. Automated diagnostic, laboratory, and pharmacy data were used to assess glycemic control, medication adherence, and preventive services.
RESULTS —This predominantly type 2 diabetic population had a mean HbA1c level of 7.8 ± 1.6%. Three-quarters of the patients received hypoglycemic agents (oral or insulin) and reported at least weekly self-monitoring of glucose and foot checks. The mean number of HbA1c tests was 2.2 ± 1.3 per year and was only slightly higher among patients with poorly controlled diabetes. Almost one-half (48.9%) had a BMI >30 kg/m2, and 47.8% of patients exercised once a week or less. Pharmacy refill data showed a 19.5% nonadherence rate to oral hypoglycemic medicines (mean 67.4 ± 74.1 days) in the prior year. Major depression was associated with less physical activity, unhealthy diet, and lower adherence to oral hypoglycemic, antihypertensive, and lipid-lowering medications. In contrast, preventive care of diabetes, including home-glucose tests, foot checks, screening for microalbuminuria, and retinopathy was similar among depressed and nondepressed patients.
CONCLUSIONS —In a primary care population, diabetes self-care was suboptimal across a continuum from home-based activities, such as healthy eating, exercise, and medication adherence, to use of preventive care. Major depression was mainly associated with patient-initiated behaviors that are difficult to maintain (e.g., exercise, diet, medication adherence) but not with preventive services for diabetes.
1,112 citations
TL;DR: Up to 21% of patients with type 2 diabetes have retinopathy at the time of first diagnosis of diabetes, and most develop some degree ofretinopathy over time, and the further complication of preretinal or vitreous hemorrhage is added.
Abstract: Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20 –74 years. During the first two decades of disease, nearly all patients with type 1 diabetes and 60% of patients with type 2 diabetes have retinopathy. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), 3.6% of younger-onset patients (type 1 diabetes) and 1.6% of olderonset patients (type 2 diabetes) were legally blind. In the younger-onset group, 86% of blindness was attributable to diabetic retinopathy. In the older-onset group, in which other eye diseases were common, one-third of the cases of legal blindness were due to diabetic retinopathy. NATURAL HISTORY OF DIABETIC RETINOPATHY Diabetic retinopathy progresses from mild nonproliferative abnormalities, characterized by increased vascular permeability, to moderate and severe nonproliferative d iabetic r etinopathy (NPDR), characterized by vascular closure, to proliferative diabetic retinopathy (PDR), characterized by the growth of new blood vessels on the retina and posterior surface of the vitreous. Macular edema, characterized by retinal thickening from leaky blood vessels, can develop at all stages of retinopathy. Pregnancy, puberty, blood glucose control, hypertension, and cataract surgery can accelerate these changes. Vision-threatening retinopathy is rare in type 1 diabetic patients in the first 3–5 years of diabetes or before puberty. During the next two decades, nearly all type 1 diabetic patients develop retinopathy. Up to 21% of patients with type 2 diabetes have retinopathy at the time of first diagnosis of diabetes, and most develop some degree of retinopathy over time. Vision loss due to diabetic retinopathy results from several mechanisms. Central vision may be impaired by macular edema or capillary nonperfusion. New blood vessels of PDR and contraction of the accompanying fibrous tissue can distort the retina and lead to tractional retinal detachment, producing severe and often irreversible vision loss. In addition, the new blood vessels may bleed, adding the further complication of preretinal or vitreous hemorrhage. Finally, neovascular glaucoma associated with PDR can be a cause of visual loss.
TL;DR: An inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans is shown and may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
Abstract: OBJECTIVE —To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity. RESEARCH DESIGN AND METHODS —We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements. RESULTS —Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11–0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≤43.9 nmol/l). This inverse association was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (log e ) was inversely associated with serum 25OHD in Mexican Americans ( P = 0.0024) and non-Hispanic whites ( P = 0.058) but not non-Hispanic blacks ( P = 0.93), adjusting for confounders. CONCLUSIONS —These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
TL;DR: Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men, and hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic Syndrome or frank diabetes and may contribute to their pathogenesis.
Abstract: OBJECTIVE —In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone–binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. RESEARCH DESIGN AND METHODS —Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. RESULTS —After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5–3.4; 1.7, 1.2–2.5; and 2.8, 1.9–4.1, respectively) and diabetes (2.3, 1.3–4.1; 1.7, 0.9–3.0; and 4.3, 2.4–7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. CONCLUSIONS —Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.
TL;DR: This review will discuss the clinical features, assessment, and management of the patient with the most common form of DN, diabetic distal sensory polyneuropathy (DPN), and the late sequelae of DPN and their prevention.
Abstract: ropathic pain (7–10), and this and other putative mechanisms will be discussed The clinical features, diagnosis, and management of the focal and multifocal neuropathies will be described A major portion of this review will discuss the clinical features, assessment, and management of the patient with the most common form of DN, diabetic distal sensory polyneuropathy (DPN) The late sequelae of DPN and their prevention will also be described Finally, practical guidelines for the screening of DPN in clinical practice will be provided For further details on this topic, please refer to recent reviews (11– 18)
TL;DR: The optimal waist circumference for diagnosing central obesity in Asians was determined and the prevalence of the metabolic syndrome in an Asian population was estimated to be comparable to that in Western populations.
Abstract: OBJECTIVE —Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS —We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18–69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS —In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18–30 years to 31.0% in those aged 60–69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P P CONCLUSIONS — NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.
TL;DR: Recommendation to increase whole-grain intake may reduce the risk of developing the metabolic syndrome and dietary glycemic index, largely attributed to the cereal fiber, is inversely associated with HOMA-IR and a lower prevalence of the metabolic Syndrome.
Abstract: OBJECTIVE —The aim of this study was to examine the relation between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. RESEARCH DESIGN AND METHODS —We examined cross-sectional associations between carbohydrate-related dietary factors, insulin resistance, and the prevalence of the metabolic syndrome in 2,834 subjects at the fifth examination (1991–1995) of the Framingham Offspring Study. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the following formula (fasting plasma insulin × plasma glucose)/22.5. The metabolic syndrome was defined using the National Cholesterol Education Program criteria. RESULTS —After adjustment for potential confounding variables, intakes of total dietary fiber, cereal fiber, fruit fiber, and whole grains were inversely associated, whereas glycemic index and glycemic load were positively associated with HOMA-IR. The prevalence of the metabolic syndrome was significantly lower among those in the highest quintile of cereal fiber (odds ratio [OR] 0.62; 95% CI 0.45–0.86) and whole-grain (0.67; 0.48–0.91) intakes relative to those in the lowest quintile category after adjustment for confounding lifestyle and dietary factors. Conversely, the prevalence of the metabolic syndrome was significantly higher among individuals in the highest relative to the lowest quintile category of glycemic index (1.41; 1.04–1.91). Total carbohydrate, dietary fiber, fruit fiber, vegetable fiber, legume fiber, glycemic load, and refined grain intakes were not associated with prevalence of the metabolic syndrome. CONCLUSIONS —Whole-grain intake, largely attributed to the cereal fiber, is inversely associated with HOMA-IR and a lower prevalence of the metabolic syndrome. Dietary glycemic index is positively associated with HOMA-IR and prevalence of the metabolic syndrome. Given that both a high cereal fiber content and lower glycemic index are attributes of whole-grain foods, recommendation to increase whole-grain intake may reduce the risk of developing the metabolic syndrome.
TL;DR: Traditional and emerging cardiac risk factors and inflammatory and prothrombotic markers were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.
Abstract: OBJECTIVE —To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association screening guidelines. RESEARCH DESIGN AND METHODS —In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50–75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission–computed tomography myocardial perfusion imaging. RESULTS —A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio [OR] 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion ( n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia. CONCLUSIONS —Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.
TL;DR: Based on this new evidence, refined the recommendations on the desired types, amounts, and intensities of aerobic physical activity for people with diabetes will now be recommended in a broader group of patients and at a broader range of intensity than done previously.
Abstract: For decades, exercise has been considered a cornerstone of diabetes management, along with diet and medication. However, high-quality evidence on the importance of exercise and fitness in diabetes was lacking until recent years. The last American Diabetes Association (ADA) technical review of exercise and type 2 diabetes (formerly known as non–insulin dependent diabetes) was published in 1990. The present work emphasizes the advances that have occurred since the last technical review was published.
Major developments since the 1990 technical review include:
Based on this new evidence, we have refined the recommendations on the desired types, amounts, and intensities of aerobic physical activity for people with diabetes. Resistance training will now be recommended in a broader group of patients and at a broader range of intensity than done previously. There are other areas in which new evidence is lacking, but we feel that previous recommendations may have been more conservative than necessary. These areas include indications for exercise stress test before beginning an exercise program and precautions regarding …
TL;DR: Estimates from a regional study carried out in the Netherlands were applied to 13 other countries, including Germany, and found that Germany had a higher prevalence of diabetes than other European countries.
Abstract: Global diabetes prevalence estimates for adults in 2000, which were derived from population-based data using oral glucose tolerance tests, were recently reported by Wild et al. (1). Because there are few OGTT-based data in the European region, estimates from a regional study carried out in the Netherlands were applied to 13 other countries, including Germany (2). For Germany, a prevalence of 4.1% was estimated, which corresponds to 2.6 …
TL;DR: It is confirmed that many patients for whom diabetes medication was prescribed were poor compliers with treatment, including both OHAs and insulin, however, electronic monitoring systems were useful in improving adherence for individual patients.
Abstract: Wens et al. (1) comment on the value of using multiple databases to search the literature for my report (2). However, they do not mention another technique that I have found to be valuable: checking the reference lists of articles found in database searches and other sources. This manual method overcomes …
TL;DR: The metabolic syndrome is inferior to established predicting models for either type 2 diabetes or CVD and combined with either predicting model did not improve the prediction of either end point.
Abstract: OBJECTIVE —The metabolic syndrome has been promoted as a method for identifying high-risk individuals for type 2 diabetes and cardiovascular disease (CVD). We therefore sought to compare this syndrome, as defined by the National Cholesterol Education Program, to the Diabetes Predicting Model and the Framingham Risk Score as predictors of type 2 diabetes and CVD, respectively. RESEARCH DESIGN AND METHODS —A population-based sample of 1,709 initially nondiabetic San Antonio Heart Study (SAHS) participants were followed for 7.5 years, 195 of whom developed type 2 diabetes. Over the same time interval, 156 of 2,570 SAHS participants experienced a cardiovascular event. A population-based sample of 1,353 initially nondiabetic Mexico City Diabetes Study (MCDS) participants were followed for 6.5 years, 125 of whom developed type 2 diabetes. Baseline measurements included medical history, age, sex, ethnicity, smoking status, BMI, blood pressure, fasting and 2-h plasma glucose levels, and fasting serum total and HDL cholesterol and triglycerides. RESULTS —The sensitivities for predicting diabetes with the metabolic syndrome were 66.2 and 62.4% in the SAHS and the MCDS, respectively, and the false-positive rates were 27.8 and 38.7%, respectively. The sensitivity and false-positive rates for predicting CVD with the metabolic syndrome in the SAHS were 67.3 and 34.2%, respectively. At corresponding false-positive rates, the two predicting models had significantly higher sensitivities and, at corresponding sensitivities, significantly lower false-positive rates than the metabolic syndrome for both end points. Combining the metabolic syndrome with either predicting model did not improve the prediction of either end point. CONCLUSIONS —The metabolic syndrome is inferior to established predicting models for either type 2 diabetes or CVD.
TL;DR: The changes in demographics, antidiabetic treatment, and glycemic control among the prevalent U.S. adult diagnosed type 2 diabetes population between the National Health and Nutrition Examination Survey (NHANES) III and the initial release of NHANES 1999-2000 are described.
Abstract: OBJECTIVE —To describe the changes in demographics, antidiabetic treatment, and glycemic control among the prevalent U.S. adult diagnosed type 2 diabetes population between the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and the initial release of NHANES 1999–2000. RESEARCH DESIGN AND METHODS —The study population was derived from NHANES III ( n = 1,215) and NHANES 1999–2000 ( n = 372) subjects who reported a diagnosis of type 2 diabetes with available data on diabetes medication and HbA 1c . Four therapeutic regimens were defined: diet only, insulin only, oral antidiabetic drugs (OADs) only, or OADs plus insulin. Multiple logistic regression was used to examine changes in antidiabetic regimens and glycemic control rates over time, adjusted for demographic and clinical risk factors. The outcome measure for glycemic control was HbA 1c . Glycemic control rates were defined as the proportion of type 2 diabetic patients with HbA 1c level RESULTS —Dietary treatment in individuals with diabetes decreased as the sole therapy from 27.4 to 20.2% between the surveys. Insulin use also decreased from 24.2 to 16.4%, while those on OADs only increased from 45.4 to 52.5%. Combination of OADs and insulin increased from 3.1 to 11.0%. Glycemic control rates declined from 44.5% in NHANES III (1988–1994) to 35.8% in NHANES 1999–2000. CONCLUSIONS —Treatment regimens among U.S. adults diagnosed with type 2 diabetes have changed substantially over the past 10 years. However, a decrease in glycemic control rates was also observed during this time period. This trend may contribute to increased rates of macrovascular and microvascular diabetic complications, which may impact health care costs. Our data support the public health message of implementation of early, aggressive management of diabetes.
TL;DR: The multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity.
Abstract: OBJECTIVE —The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up. RESEARCH DESIGN AND METHODS —We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development. RESULTS —Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3–2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA 1c ) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development. CONCLUSIONS —The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.
TL;DR: There are several classes of medications that can be used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes, including statins, fibrates, niacin, and thiazolidinediones, which show significant improvement in coronary artery disease after diabetic dyslipidemia treatment.
Abstract: Insulin resistance and type 2 diabetes are associated with a clustering of interrelated plasma lipid and lipoprotein abnormalities, which include reduced HDL cholesterol, a predominance of small dense LDL particles, and elevated triglyceride levels. Each of these dyslipidemic features is associated with an increased risk of cardiovascular disease. Increased hepatic secretion of large triglyceride-rich VLDL and impaired clearance of VLDL appears to be of central importance in the pathophysiology of this dyslipidemia. Small dense LDL particles arise from the intravascular processing of specific larger VLDL precursors. Typically, reduced plasma HDL levels in type 2 diabetes are manifest as reductions in the HDL(2b) subspecies and relative or absolute increases in smaller denser HDL(3b) and HDL(3c). Although behavioral interventions such as diet and exercise can improve diabetic dyslipidemia, for most patients, pharmacological therapy is needed to reach treatment goals. There are several classes of medications that can be used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes, including statins, fibrates, niacin, and thiazolidinediones. Clinical trials have shown significant improvement in coronary artery disease after diabetic dyslipidemia treatment.
TL;DR: Beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD, there is a growing recognition, however, that edema can occur in patients treated with either drug.
Abstract: Diabetes is a chronic, progressively worsening disease associated with a variety of microvascular and macrovascular complications. Cardiovascular disease (CVD) is the main cause of death in these patients (1,2). During the past decade, numerous drugs have been introduced for the treatment of type 2 diabetes that, used in monotherapy or in combination therapy, are effective in lowering blood glucose to achieve glycemic goals and in reducing diabetes-related end-organ disease.
Two such drugs, rosiglitazone and pioglitazone, belong to the class called thiazolidinediones (TZDs) (3). Troglitazone, the first agent of this class to be approved, was effective in controlling glycemia but was removed from the market because of serious liver toxicity. Both rosiglitazone and pioglitazone are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and a single agent do not result in adequate glycemic control (4) (package insert Avandia [rosiglitazone maleate; GlaxoSmithKline] and Actos (5) [pioglitazone hydrochloride; Takeda Pharmaceuticals]). In addition to lowering blood glucose, both drugs may benefit cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function, and fibrinolytic status (6,7).
These beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD. There is a growing recognition, however, that edema can occur in patients treated with either drug. Because people with diabetes are at increased risk for CVD and many have preexisting heart disease, the edema that sometimes accompanies the use of a TZD can be cause for concern, as it may be a harbinger or sign of congestive heart failure (CHF). An analysis of Medicare beneficiaries hospitalized with the diagnosis of diabetes and CHF indicated that the number of these patients discharged on TZDs had increased from …
TL;DR: The newest American Diabetes Association consensus statement on peripheral arterial disease (PAD) in diabetic patients with great interest recommended that “a screening ABI (ankle-brachial index) should be performed in patients >50 years of age.
Abstract: As a general internist, I read the newest American Diabetes Association consensus statement (1) on peripheral arterial disease (PAD) in diabetic patients with great interest. In the statement, it is recommended that “a screening ABI (ankle-brachial index) should be performed in patients >50 years of …
TL;DR: There is a need to provide more intensive education before fasting, to disseminate guidelines, and to propose further studies assessing the impact of fasting on morbidity and mortality.
Abstract: OBJECTIVE —The aim of this study was to assess the characteristics and care of patients with diabetes in countries with a sizable Muslim population and to study diabetes features during Ramadan and the effect of fasting. RESEARCH DESIGN AND METHODS —This was a population-based, retrospective, transversal survey conducted in 13 countries. A total of 12,914 patients with diabetes were recruited using a stratified sampling method, and 12,243 were considered for the analysis. RESULTS —Investigators recruited 1,070 (8.7%) patients with type 1 diabetes and 11,173 (91.3%) patients with type 2 diabetes. During Ramadan, 42.8% of patients with type 1 diabetes and 78.7% with type 2 diabetes fasted for at least 15 days. Less than 50% of the whole population changed their treatment dose (approximately one-fourth of patients treated with oral antidiabetic drugs [OADs] and one-third of patients using insulin). Severe hypoglycemic episodes were significantly more frequent during Ramadan compared with other months (type 1 diabetes, 0.14 vs. 0.03 episode/month, P = 0.0174; type 2 diabetes, 0.03 vs. 0.004 episode/month, P CONCLUSIONS —The large proportion of both type 1 and type 2 diabetic subjects who fast during Ramadan represent a challenge to their physicians. There is a need to provide more intensive education before fasting, to disseminate guidelines, and to propose further studies assessing the impact of fasting on morbidity and mortality.
TL;DR: Depression for those with diabetes is an important comorbidity that requires careful management because of its severe impact on quality of life.
Abstract: OBJECTIVE —The aim of the study was to assess the prevalence of diabetes and depression and their associations with quality of life using a representative population sample. RESEARCH DESIGN AND METHODS —The study consisted of a representative population sample of individuals aged ≥15 years living in South Australia comprising 3,010 personal interviews conducted by trained health interviewers. The prevalence of depression in those suffering doctor-diagnosed diabetes and comparative effects of diabetic status and depression on quality-of-life dimensions were measured. RESULTS —The prevalence of depression in the diabetic population was 24% compared with 17% in the nondiabetic population. Those with diabetes and depression experienced an impact with a large effect size on every dimension of the Short Form Health-Related Quality-of-Life Questionnaire (SF-36) as compared with those who suffered diabetes and who were not depressed. A supplementary analysis comparing both depressed diabetic and depressed nondiabetic groups showed there were statistically significant differences in the quality-of-life effects between the two depressed populations in the physical and mental component summaries of the SF-36. CONCLUSIONS —Depression for those with diabetes is an important comorbidity that requires careful management because of its severe impact on quality of life.
TL;DR: The interaction between physical activity and fitness suggests that the potential beneficial effect of activity may be greatest in children with lower cardiorespiratory fitness, and physical activity is inversely associated with metabolic risk, independently of potential confounders.
Abstract: OBJECTIVE —Features of the metabolic syndrome are becoming increasingly evident in children. Decreased physical activity is likely to be an important etiological factor, as shown previously for subjective measures of physical activity in selected groups. The purpose of this study was to examine the relationship between the metabolic syndrome and objectively measured physical activity and whether fitness modified this relationship. RESEARCH DESIGN AND METHODS —A total of 589 Danish children (310 girls, 279 boys, mean [±SD] age 9.6 ± 0.44 years, mean weight 33.6 ± 6.4 kg, mean height 1.39 ± 0.06 m) were randomly selected. Physical activity was measured with the uni-axial Computer Science & Applications accelerometer (MTI actigraph) worn at the hip for at least 3 days (≥10 h/day) and fitness with a maximal bike test. As outcomes, we measured sitting systolic and diastolic blood pressure, degree of adiposity (sum of four skinfolds), and, finally, insulin, glucose, triglicerides, and HDL cholesterol in fasting blood samples. The outcome variables were statistically normalized and expressed as the number of SDs from the mean. (i.e., Z scores). A metabolic syndrome risk score was computed as the mean of these Z scores. Multiple linear regression was used to test the association between physical activity and metabolic risk, adjusted primarily for age, sex, sexual maturation, ethnicity, parental smoking, socioeconomic factors, and the Computer Science & Applications unit, as well as for fitness. Robust SEs were computed by clustering on school. RESULTS —All children were in the nondiabetic range of fasting glucose. Metabolic risk was inversely related to physical activity ( P = 0.008). The relationship was weakened after adjustment for fitness, but there was a significantly positive interaction between physical activity and fitness. CONCLUSIONS —Physical activity is inversely associated with metabolic risk, independently of potential confounders. The interaction between physical activity and fitness suggests that the potential beneficial effect of activity may be greatest in children with lower cardiorespiratory fitness.