Showing papers in "Diabetes Care in 2001"

Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome

Abstract: OBJECTIVE —To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization (WHO) RESEARCH DESIGN AND METHODS —A total of 4,483 subjects aged 35–70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome In subjects who had type 2 diabetes ( n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) ( n = 798), or insulin-resistance with normal glucose tolerance (NGT) ( n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 69 years RESULTS —In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome ( P P P = 0002) CONCLUSIONS —The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from different studies

The Prevalence of Comorbid Depression in Adults With Diabetes: A meta-analysis

Abstract: OBJECTIVE —To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS —MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used χ 2 statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS —A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8–2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS —The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Effectiveness of Self-Management Training in Type 2 Diabetes: A systematic review of randomized controlled trials

Abstract: OBJECTIVE —To systematically review the effectiveness of self-management training in type 2 diabetes. RESEARCH DESIGN AND METHODS —MEDLINE, Educational Resources Information Center (ERIC), and Nursing and Allied Health databases were searched for English-language articles published between 1980 and 1999. Studies were original articles reporting the results of randomized controlled trials of the effectiveness of self-management training in people with type 2 diabetes. Relevant data on study design, population demographics, interventions, outcomes, methodological quality, and external validity were tabulated. Interventions were categorized based on educational focus (information, lifestyle behaviors, mechanical skills, and coping skills), and outcomes were classified as knowledge, attitudes, and self-care skills; lifestyle behaviors, psychological outcomes, and quality of life; glycemic control; cardiovascular disease risk factors; and economic measures and health service utilization. RESULTS —A total of 72 studies described in 84 articles were identified for this review. Positive effects of self-management training on knowledge, frequency and accuracy of self-monitoring of blood glucose, self-reported dietary habits, and glycemic control were demonstrated in studies with short follow-up ( CONCLUSIONS —Evidence supports the effectiveness of self-management training in type 2 diabetes, particularly in the short term. Further research is needed to assess the effectiveness of self-management interventions on sustained glycemic control, cardiovascular disease risk factors, and ultimately, microvascular and cardiovascular disease and quality of life.

Projection of Diabetes Burden Through 2050: Impact of changing demography and disease prevalence in the U.S.

Abstract: OBJECTIVE —To project the number of people with diagnosed diabetes in the U.S. through 2050, accounting for changing demography and diabetes prevalence rates. RESEARCH DESIGN AND METHODS —We combined age-, sex-, and race-specific diagnosed diabetes prevalence rates—predicted from 1980–1998 trends in prevalence data from the National Health Interview Survey—with Bureau of Census population demographic projections. Sensitivity analyses were performed by varying both prevalence rate and population projections. RESULTS —The number of Americans with diagnosed diabetes is projected to increase 165%, from 11 million in 2000 (prevalence of 4.0%) to 29 million in 2050 (prevalence of 7.2%). The largest percent increase in diagnosed diabetes will be among those aged ≥75 years (+271% in women and +437% in men). The fastest growing ethnic group with diagnosed diabetes is expected to be black males (+363% from 2000–2050), with black females (+217%), white males (+148%), and white females (+107%) following. Of the projected 18 million increase in the number of cases of diabetes in 2050, 37% are due to changes in demographic composition, 27% are due to population growth, and 36% are due to increasing prevalence rates. CONCLUSIONS —If recent trends in diabetes prevalence rates continue linearly over the next 50 years, future changes in the size and demographic characteristics of the U.S. population will lead to dramatic increases in the number of Americans with diagnosed diabetes.

Interventions to Improve the Management of Diabetes in Primary Care, Outpatient, and Community Settings: A systematic review

Abstract: OBJECTIVE —To review the effectiveness of interventions targeted at health care professionals and/or the structure of care in order to improve the management of diabetes in primary care, outpatient, and community settings. RESEARCH DESIGN AND METHODS —A systematic review of controlled trials evaluating the effectiveness of interventions targeted at health care professionals and aimed at improving the process of care or patient outcomes for patients with diabetes was performed. Standard search methods of the Cochrane Effective Practice and Organization of Care Group were used. RESULTS —A total of 41 studies met the inclusion criteria. The studies identified were heterogeneous in terms of interventions, participants, settings, and reported outcomes. In all studies, the interventions were multifaceted. The interventions were targeted at health care professionals only in 12 studies, at the organization of care only in 9 studies, and at both in 20 studies. Complex professional interventions improved the process of care, but the effect on patient outcomes remained less clear because such outcomes were rarely assessed. Organizational interventions that facilitated the structured and regular review of patients also showed a favorable effect on process measures. Complex interventions in which patient education was added and/or the role of a nurse was enhanced led to improvements in patient outcomes as well as the process of care. CONCLUSIONS —Multifaceted professional interventions and organizational interventions that facilitate structured and regular review of patients were effective in improving the process of care. The addition of patient education to these interventions and the enhancement of the role of nurses in diabetes care led to improvements in patient outcomes and the process of care.

A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test

Abstract: OBJECTIVE —Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. RESEARCH DESIGN AND METHODS —OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI 2 ), 38 obese nondiabetic subjects (BMI > 25 kg/m 2 ), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU · min − 1 · m − 2 insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP ), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). RESULTS —OGIS and Cl CLAMP were correlated in the whole group ( R = 0.77, P R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P R = 0.65, P CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 ± 16 vs. 362 ± 11 ml · min − 1 · m − 2 , P P P CLAMP ). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. CONCLUSIONS —OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.

Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers : A Prospective Randomized Multicenter Clinical Trial

Abstract: OBJECTIVE — We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. RESEARCH DESIGN AND METHODS — In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. RESULTS — At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group ( P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group ( P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. CONCLUSIONS — Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.

Diagnosing Insulin Resistance in the General Population

Abstract: OBJECTIVE —Difficulties in measuring insulin sensitivity prevent the identification of insulin-resistant individuals in the general population. Therefore, we compared fasting insulin, homeostasis model assessment (HOMA), insulin-to-glucose ratio, Bennett index, and a score based on weighted combinations of fasting insulin, BMI, and fasting triglycerides with the euglycemic insulin clamp to determine the most appropriate method for assessing insulin resistance in the general population. RESEARCH DESIGN AND METHODS —Family history of diabetes, BMI, blood pressure, waist and hip circumference, fasting lipids, glucose, insulin, liver enzymes, and insulin sensitivity index (ISI) using the euglycemic insulin clamp were obtained for 178 normoglycemic individuals aged 25–68 years. Product-moment correlations were used to examine the association between ISI and various surrogate measurements of insulin sensitivity. Regression models were used to devise weights for each variable and to identify cutoff points for individual components of the score. A bootstrap procedure was used to identify the most useful predictors of ISI. RESULTS —Correlation coefficients between ISI and fasting insulin, HOMA, insulin-to-glucose ratio, and the Bennett index were similar in magnitude. The variables that best predicted insulin sensitivity were fasting insulin and fasting triglycerides. The use of a score based on \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[Mffm{/}I{\,}{\,}{=}{\,}{\,}exp{[}2.63{\,}{\,}{-}{\,}{\,}0.28ln(insulin){\,}{\,}{-}{\,}{\,}0.31ln(TAG){]}\] \end{document} rather than the use of fasting insulin alone resulted in a higher sensitivity and a maintained specificity when predicting insulin sensitivity. CONCLUSIONS —A weighted combination of two routine laboratory measurements, i.e., fasting insulin and triglycerides, provides a simple means of screening for insulin resistance in the general population.

Peripheral arterial disease in diabetic and nondiabetic patients: A comparison of severity and outcome

Abstract: OBJECTIVE —The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients. RESEARCH DESIGN AND METHODS —Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died. RESULTS —A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean ± SD) of the patients was 64.7 ± 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 ± 10.4 vs. 65.3 ± 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee ( P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 ± 11.4 vs. 71.1 ± 8.7 years, P = 0.04). CONCLUSIONS —In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.

Platelet Dysfunction in Type 2 Diabetes

Abstract: Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI(2)) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI(2) and enhances endothelial generation of PGI(2) and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.

Diastolic Dysfunction in Normotensive Men with Well-Controlled Type 2 Diabetes: Importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy

Abstract: OBJECTIVE — Because a pseudonormal pattern of ventricular filling has never been considered in studies that reported a prevalence of left ventricular diastolic dysfunction (LVDD) between 20 and 40%, our aim was to more completely evaluate the prevalence of LVDD in subjects with diabetes. RESEARCH DESIGN AND METHODS — We studied 46 men with type 2 diabetes who were aged 38-67 years; without evidence of diabetic complications, hypertension, coronary artery disease, congestive heart failure, or thyroid or overt renal disease; and with a maximal treadmill exercise test showing no ischemia. LVDD was evaluated by Doppler echocardiography, which included the use of the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of left ventricular filling. RESULTS — LVDD was found in 28 subjects (60%), of whom 13 (28%) had a pseudonormal pattern of ventricular filling and 15 (32%) had impaired relaxation. Systolic function was normal in all subjects, and there was no correlation between LVDD and indexes of metabolic control. CONCLUSIONS — LVDD is much more common than previously reported in subjects with well-controlled type 2 diabetes who are free of clinically detectable heart disease. The high prevalence of this phenomenon in this high-risk population suggests that screening for LVDD in type 2 diabetes should include procedures such as the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of ventricular filling.

Management of Hyperglycemic Crises in Patients With Diabetes

Abstract: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two of the most serious acute complications of diabetes. These hyperglycemic emergencies continue to be important causes of morbidity and mortality among patients with diabetes in spite of major advances in the understanding of their pathogenesis and more uniform agreement about their diagnosis and treatment. The annual incidence rate for DKA estimated from population-based studies ranges from 4.6 to 8 episodes per 1,000 patients with diabetes (1,2), and in more recent epidemiological studies in the U.S., it was estimated that hospitalizations for DKA during the past two decades are increasing (3). Currently, DKA appears in 4-9% of all hospital discharge summaries among patients with diabetes (4,5). The incidence of HHS is difficult to determine because of the lack of population-based studies and the multiple combined illnesses often found in these patients. In general, it is estimated that the rate of hospital admissions due to HHS is lower than the rate due to DKA and accounts for <1% of all primary diabetic admissions (4,5,6). Treatment of patients with DKA and HHS uses significant health care resources, which increases health care costs. In 1983, the cost of hospitalization for DKA in Rhode Island for 1 year was estimated to be $225 million (2). It was recently reported that treatment of DKA episodes represents more than one of every four health care dollars spent on direct medical care for adult patients with type 1 diabetes and for one of every two dollars in those patients experiencing multiple episodes of ketoacidosis (7). Based on an annual average of ∼100,000 hospitalizations for DKA in the U.S. (4) and estimated annual mean medical care charges of ∼$13,000 per patient experiencing a DKA episode (7), the annual hospital cost for patients …

Type 1 and Type 2 Diabetes and Incident Hip Fractures in Postmenopausal Women

Abstract: OBJECTIVE —To examine whether postmenopausal women with diabetes experienced a higher incidence of hip fracture than women without diabetes. RESEARCH DESIGN AND METHODS —A prospective cohort of 32,089 postmenopausal women residing in Iowa were surveyed by mail in 1986 and followed for 11 years. Diabetes status and other potential risk factors were assessed by questionnaires at baseline; incidence of hip fracture was ascertained by follow-up questionnaires. RESULTS —A total of 490 hip fractures were reported over 306,900 person-years of follow-up. After adjustment for age, smoking status, estrogen use, BMI, and waist-to-hip ratio, women with type 1 diabetes ( n = 47) were 12.25 times (95% CI 5.05–29.73) more likely to report an incident hip fracture than women without diabetes. Women with type 2 diabetes had a 1.70-fold higher risk (1.21–2.38) of incident hip fracture than women without diabetes. Longer duration of type 2 diabetes was associated with higher incidence, as was use of insulin or oral diabetes medications in women with type 2 diabetes. Furthermore, women who were initially free of diabetes but in whom diabetes developed had a relative risk of hip fracture of 1.60 (1.14–2.25) compared with women who never had diabetes. CONCLUSIONS —Postmenopausal women who have diabetes or in whom diabetes develops are at higher risk for hip fracture than nondiabetic postmenopausal women. Strategies to prevent osteoporosis and/or falling may be especially warranted in women with diabetes.

Congestive Heart Failure in Type 2 Diabetes: Prevalence, incidence, and risk factors

Abstract: OBJECTIVE —To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS —We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF. RESULTS —CHF was prevalent in 11.8% ( n = 1,131) of diabetic subjects and 4.5% ( n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF. CONCLUSIONS —Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.

Renal Gluconeogenesis Its importance in human glucose homeostasis

Abstract: Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently, however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.

Off-Loading the Diabetic Foot Wound: A randomized clinical trial

Abstract: OBJECTIVE —To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes. RESEARCH DESIGN AND METHODS —In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day). RESULTS —The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1–26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW ( P = 0.033) and half-shoe ( P = 0.012). Patients were significantly less active in the TCC (600.1 ± 320.0 daily steps) compared with the half-shoe (1,461.8 ± 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 ± 563.3 daily steps, P = 0.67) or the RCW and the half-shoe ( P = 0.15). CONCLUSIONS —The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe.

A Comparison of Two Diabetic Foot Ulcer Classification Systems The Wagner and the University of Texas wound classification systems

Abstract: OBJECTIVE — In this study, the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (UT) (grade and stage) wound classification systems. RESEARCH DESIGN AND METHODS — Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded, and patients were followed up until healing or for 6 months. RESULTS — Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm 2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5 (3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade ( P P < 0.0001) and stage ( P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P < 0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001), but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner ( P = 0.1) or the UT system ( P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system ( P P < 0.05). CONCLUSIONS — Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system9s inclusion of stage makes it a better predictor of outcome.

Basal Insulin Therapy in Type 2 Diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin

Abstract: OBJECTIVE—To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS—A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily (n = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose RESULTS—The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means ± SD) in HbA1c from baseline to end point was similar in the insulin glargine group (−0.41 ± 0.1%) and the NPH group (−0.59 ± 0.1%) after patients began with an average baseline HbA1c of ∼8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.8%). However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase (26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P CONCLUSIONS—In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine demonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.

Simple Screening Tests for Peripheral Neuropathy in the Diabetes Clinic

Abstract: OBJECTIVE — The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy. RESEARCH DESIGN AND METHODS — We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test. RESULTS — The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively. The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring ∼60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test. CONCLUSIONS — Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.

Limitations of Conventional Methods of Self-Monitoring of Blood Glucose: Lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes

Abstract: OBJECTIVE —Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA 1c measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring. RESEARCH DESIGN AND METHODS —A total of 56 children with type 1 diabetes (age 2–18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified. RESULTS —Despite satisfactory HbA 1c levels (7.7 ± 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose CONCLUSIONS —Despite excellent HbA 1c levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.

Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity.

Abstract: Lifestyle factors related to obesity, eating behavior, and physical activity play a major role in the prevention and treatment of type 2 diabetes. In recent years, there has been progress in the development of behavioral strategies to modify these lifestyle behaviors. Further research, however, is clearly needed, because the rates of obesity in our country are escalating, and changing behavior for the long term has proven to be very difficult. This review article, which grew out of a National Institute of Diabetes and Digestive and Kidney Diseases conference on behavioral science research in diabetes, identifies four key topics related to obesity and physical activity that should be given high priority in future research efforts: 1) environmental factors related to obesity, eating, and physical activity; 2) adoption and maintenance of healthful eating, physical activity, and weight; 3) etiology of eating and physical activity; and 4) multiple behavior changes. This review article discusses the significance of each of these four topics, briefly reviews prior research in each area, identifies barriers to progress, and makes specific research recommendations.

Relationships of Upper Gastrointestinal Motor and Sensory Function With Glycemic Control

Abstract: Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may, accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.

Chronic Care Clinics for Diabetes in Primary Care A system-wide randomized trial

Abstract: OBJECTIVE —To evaluate the impact of primary care group visits (chronic care clinics) on the process and outcome of care for diabetic patients. RESEARCH DESIGN AND METHODS —We evaluated the intervention in primary care practices randomized to intervention and control groups in a large-staff model health maintenance organization (HMO). Patients included diabetic patients ≥30 years of age in each participating primary care practice, selected at random from an automated diabetes registry. Primary care practices were randomized within clinics to either a chronic care clinic (intervention) group or a usual care (control) group. The intervention group conducted periodic one-half day chronic care clinics for groups of ∼8 diabetic patients in their respective doctor’s practice. Chronic care clinics consisted of standardized assessments; visits with the primary care physician, nurse, and clinical pharmacist; and a group education/peer support meeting. We collected self-report questionnaires from patients and data from administrative systems. The questionnaires were mailed, and telephoned interviews were conducted for nonrespondents, at baseline and at 12 and 24 months; we queried the process of care received, the satisfaction with care, and the health status of each patient. Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems. RESULTS —In an intention-to-treat analysis at 24 months, the intervention group had received significantly more recommended preventive procedures and helpful patient education. Of five primary health status indicators examined, two (SF-36 general health and bed disability days) were significantly better in the intervention group. Compared with control patients, intervention patients had slightly more primary care visits, but significantly fewer specialty and emergency room visits. Among intervention participants, we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes, including patient satisfaction and HbA1c levels. CONCLUSIONS —Periodic primary care sessions organized to meet the complex needs of diabetic patients improved the process of diabetes care and were associated with better outcomes.

Impaired Autonomic Function Is Associated With Increased Mortality, Especially in Subjects With Diabetes, Hypertension, or a History of Cardiovascular Disease: The Hoorn Study

Abstract: OBJECTIVE —Measures of baroreflex sensitivity, heart rate variability (HRV), and the classical Ewing test parameters are currently used for the diagnosis of diabetic autonomic neuropathy and for mortality risk stratification after myocardial infarction. However, the strengths of the associations of these measures of autonomic function with risk of mortality have never been compared in one study population. Furthermore, no evidence is available on the possible effect of glucose tolerance on these associations. RESEARCH DESIGN AND METHODS —The study population ( n = 605) consisted of a glucose tolerance–stratified sample from a general population (50–75 years of age). Cardiac cycle duration and continuous finger arterial pressure were measured under two conditions: at rest and on metronome breathing. From these readings, seven parameters of autonomic function were assessed (one Ewing, five HRV, and one baroreflex sensitivity). RESULTS —During 9 years of follow-up, 101 individuals died, 43 from cardiovascular causes. Subjects with diabetes and low levels of the autonomic function parameters, indicating impaired autonomic function, had an approximately doubled risk of mortality. This association was consistent, though not statistically significant, for all parameters. The elevated risk was not observed in subjects without diabetes, hypertension, or prevalent cardiovascular disease. CONCLUSIONS —Impaired autonomic function is associated with all-cause and cardiovascular mortality. Moreover, the results of the present study suggest that cardiac autonomic dysfunction in patients already at risk (diabetes, hypertension, or history of cardiovascular disease) may be especially hazardous.

Clinical and Psychological Course of Diabetes From Adolescence to Young Adulthood: A longitudinal cohort study

Abstract: OBJECTIVE —To determine the clinical and psychological course of diabetes through adolescence and the relationship with glycemic control in young adulthood. RESEARCH DESIGN AND METHODS —A longitudinal cohort study of adolescents recruited from the register of the outpatient pediatric diabetes clinic. A total of 76 individuals (43 male patients, 33 female patients) aged 11–18 years completed baseline assessments, and 65 individuals (86%) were reinterviewed as young adults (20–28 years of age). Longitudinal assessments were made of glycemic control (HbA 1c ), weight gain (BMI), and development of complications. Adolescents completed self-report questionnaires to assess emotional and behavioral problems as well as self-esteem. As young adults, psychological state was assessed by the Revised Clinical Interview Schedule and the self-report Brief Symptom Inventory. RESULTS —Mean HbA 1c levels peaked in late adolescence and were worse in female participants (average 11.1% at 18–19 years of age). The proportion of individuals who were overweight (BMI >25.0 kg/m 2 ) increased during the 8-year period from 21 to 54% in female patients and from 2 to 28% in male patients. Serious diabetes-related events included death in one patient and cognitive impairment in two patients. Individuals in whom diabetic complications developed (25% of male patients and 38% of female patients) had significantly higher mean HbA 1c levels than those without complications (difference 1.9%, 95% CI 1.1–2.7, P 1c during the subsequent 8 years (β = 0.15, SEM (β) 0.04, P CONCLUSIONS —The outcome for this cohort was generally poor. Behavioral problems in adolescence seem to be important in influencing later glycemic control.

Improved Glycemic Control and Enhanced Insulin Sensitivity in Type 2 Diabetic Subjects Treated With Pioglitazone

Abstract: OBJECTIVE —To elucidate the effects of pioglitazone treatment on glucose and lipid metabolism in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS —A total of 23 diabetic patients (age 30–70 years, BMI 2 ) who were being treated with a stable dose of sulfonylurea were randomly assigned to receive either placebo ( n = 11) or pioglitazone (45 mg/day) ( n = 12) for 16 weeks. Before and after 16 weeks of treatment, all subjects received a 75-g oral glucose tolerance test (OGTT); and hepatic and peripheral insulin sensitivity was measured with a two-step euglycemic insulin (40 and 160 mU · min − 1 · m –2 ) clamp performed with 3-[ 3 H]glucose and indirect calorimetry. HbA 1c was measured monthly throughout the study period. RESULTS —After 16 weeks of pioglitazone treatment, the fasting plasma glucose (FPG; 184 ± 15 to 135 ± 11 mg/dl, P P 1c (8.9 ± 0.3 to 7.2 ± 0.5%, P P P r = 0.67, P P P CONCLUSIONS —These results suggest that pioglitazone therapy in type 2 diabetic patients decreases fasting and postprandial plasma glucose levels by improving hepatic and peripheral (muscle) tissue sensitivity to insulin.

Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes.

Abstract: OBJECTIVE — To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS — The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (∼1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS — Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before ( r = -0.613, P < 0.0001) and after ( r = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 ± 0.12 vs. -0.79 ± 0.09, F = 0.25, P = 0.61) nor the intercepts ( y -intercept = 1.67 vs. 1.70, x -intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment ( r = -0.617, P CONCLUSIONS — HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.

Dietary Fat and Incidence of Type 2 Diabetes in Older Iowa Women

Abstract: OBJECTIVE —To examine the associations between reported intakes of dietary fat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS —We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up. RESULTS —After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with ω-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 ( P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score. CONCLUSIONS —These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.

The Diabetes Network Internet-Based Physical Activity Intervention: A randomized pilot study

Abstract: OBJECTIVE —Because of other competing priorities, physical activity (PA) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels. RESEARCH DESIGN AND METHODS —A total of 78 type 2 diabetic patients (53% female, average age 52.3 years) were randomized to the Diabetes Network (D-Net) Active Lives PA Intervention or an Internet information-only condition. The intervention condition received goal-setting and personalized feedback, identified and developed strategies to overcome barriers, received and could post messages to an on-line “personal coach,” and were invited to participate in peer group support areas. Key outcomes included minutes of PA per week and depressive symptomatology. RESULTS —There was an overall moderate improvement in PA levels within both intervention and control conditions, but there was no significant improvement in regard to condition effects. There was substantial variability in both site use and outcomes within the intervention and control conditions. Internal analyses revealed that among intervention participants, those who used the site more regularly derived significantly greater benefits, whereas those in the control condition derived no similar benefits with increased program use. CONCLUSIONS —Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions. We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time.

Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance.

Abstract: Recent evidence derived from four independent methods indicates that an excess triglyceride storage within skeletal muscle is linked to insulin resistance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid oxidation during postabsorptive conditions are prominent, leading to diminished use of fatty acids and increased esterification and storage of lipid within skeletal muscle. These impairments in fatty acid metabolism during fasting conditions may be related to a metabolic inflexibility in insulin resistance that is not limited to defects in glucose metabolism during insulin-stimulated conditions. Thus, there is substantial evidence implicating perturbations in fatty acid metabolism during accumulation of skeletal muscle triglyceride and in the pathogenesis of insulin resistance. Weight loss by caloric restriction improves insulin sensitivity, but the effects on fatty acid metabolism are less conspicuous. Nevertheless, weight loss decreases the content of triglyceride within skeletal muscle, perhaps contributing to the improvement in Insulin action with weight loss. Alterations in skeletal muscle substrate metabolism provide insight into the link between skeletal muscle triglyceride accumulation and insulin resistance, and they may lead to more appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.