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Aims/hypothesis: Hyperglycaemia is a risk factor for cardiovascular disease (CVD) and all-cause mortality in individuals without diabetes. We investigated: (1) whether the risk of all-cause and CVD mortality extended continuously throughout the range of fasting plasma glucose (FPG), 2 h plasma glucose (2hPG) and HbA(1c) values; and (2) the ability of these measures to improve risk prediction for mortality., Methods: Data on 10,026 people aged >or=25 years without diagnosed diabetes were obtained from the population-based Australian Diabetes, Obesity and Lifestyle study. Between 1999 and 2000, FPG, 2hPG and HbA(1c) were assessed and all-cause (332 deaths) and CVD (88 deaths) mortality were obtained after 7 years., Results: Both 2hPG and HbA(1c) exhibited linear relationships with all-cause and CVD mortality, whereas FPG showed J-shaped relationships. The adjusted HR (95% CI) for all-cause mortality per SD increase was 1.2 (1.1-1.3) for 2hPG and 1.1 (1.0-1.2) for HbA(1c). The HR for FPG <5.1 mmol/l (per SD decrease) was 2.0 (1.3-3.0); for FPG >or=5.1 mmol/l (per SD increase) the HR was 1.1 (1.0-1.2). Corresponding HRs for CVD mortality were 1.2 (1.0-1.4), 1.2 (1.0-1.3), 4.0 (2.1-7.6) and 1.3 (1.1-1.4). The discriminative ability of each measure was similar; no measure substantially improved individual risk identification over traditional risk factors., Conclusions/interpretation: In individuals without diagnosed diabetes, 2hPG and FPG, but not HbA(1c) were significant predictors of all-cause mortality, whereas all measures were significant predictors of CVD mortality. However, these glucose measures did not substantially improve individual risk identification.

Background: Despite having lower average body mass indexes (BMIs) than do whites, Asians are at high risk of type 2 diabetes, possibly because of their greater central adiposity. The criteria for identifying individuals at risk of obesity-related conditions are usually not population specific., Objective: Our goal was to determine whether the National Heart, Lung, and Blood Institute (NHLBI) overweight and obesity guidelines are useful for identifying diabetes risk in Japanese Americans., Design: This was a prospective, cohort study of 466 nondiabetic Japanese Americans [age: 52.2 +/- 0.6 y; BMI (in kg/m(2)): 24.1 +/- 0.2; +/- SEM]. Diabetes status at a 5-y follow-up visit was assessed with an oral-glucose-tolerance test., Results: Among 240 subjects aged < or = 55 y, incident diabetes was strongly associated with overweight (BMI > or = 25) at baseline [relative risk (RR): 22.4; 95% CI: 2.7, 183; adjusted for age, sex, smoking, and family history] and weight gain of > 10 kg since the age of 20 y (adjusted RR: 4.5; 95% CI: 1.4, 14.5). NHLBI definitions of central obesity (waist circumference > or = 88 cm for women and > or = 102 cm for men) were unsuitable for this population because only 15 of 240 subjects met these criteria. A waist circumference greater than or equal to the third tertile was associated with diabetes (adjusted RR: 5.4; 95% CI: 1.7, 17.0). Among 226 subjects aged >55 y, incident diabetes was not associated with BMI, weight gain, or waist circumference., Conclusions: NHLBI definitions are useful for identifying overweight Japanese Americans aged < 55 y who are at high risk of diabetes. Although central adiposity is an important risk factor, the guidelines for waist circumference are insensitive predictors of diabetes risk in this population.

Objective: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified., Research Design and Methods: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals., Results: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values., Conclusions: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.

Objective: Plasma leptin levels correlate strongly with increased total adipose tissue, a known risk factor for type 2 diabetes, yet the role of leptin in the etiology of diabetes remains unclear. We sought to determine whether leptin is a risk factor for development of diabetes in Japanese Americans., Research Design and Methods: We compared baseline leptin levels in 370 nondiabetic Japanese Americans who remained nondiabetic for 5-6 years of follow-up with those of 40 nondiabetic Japanese Americans who developed diabetes during follow-up. All participants had computed tomography measurements of baseline subcutaneous chest, abdomen, thigh, and intra-abdominal fat, with total fat defined as the sum of all these measurements., Results: The mean age was 51.7 +/- 11.7 years for men and 51.9 +/- 12.0 years for women. The 23 men who developed diabetes had significantly higher leptin levels than the 212 men who remained nondiabetic (P < 0.01). Among men, baseline leptin levels predicted diabetes risk independent of baseline total fat, insulin, insulin resistance, glucose, or age in separate multiple logistic regression models (relative risk adjusted for baseline total fat = 1.80 per SD increase [2.7 ng/ml], 95% CI 1.02-3.17). This association was particularly strong among men in the top decile for intra-abdominal fat. In contrast, the 17 women who developed diabetes had leptin levels similar to those of the 158 women who remained nondiabetic (P = 0.31)., Conclusions: Among Japanese Americans, increased baseline leptin levels are associated with increased risk of developing diabetes in men but not in women.

Objective: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings., Research Design and Methods: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed., Results: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot., Conclusions: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.

We examined neuropathy, ankle pressure index (API), and other factors as predictors of transcutaneous oxygen (TcPO2) in the lower limbs of 657 diabetic subjects. Eligible subjects underwent a clinical assessment that included three standard measures of autonomic neuropathy. TcPO2 measurements were performed at 37 degrees C and 44 degrees C at four lower limb locations. Associations between potential predictors and TcPO2 were tested using univariate and multivariate statistics. Mean TcPO2 at any site did not differ by presence of autonomic neuropathy at either temperature, except for a significantly lower value at 44 degrees C below the knee (56.5 versus 59.2 mmHg, p = 0.021). In multivariate analysis, autonomic neuropathy was significantly and independently related to leg 44 degrees C TcPO2 only (coefficient = -2.6734, p = 0.0182). Much stronger associations were seen between TcPO2 and age, ankle blood pressure, and relative body weight on the plantar foot; and between API, glycosylated haemoglobin, ankle blood pressure, and pedal oedema on the dorsal foot and leg. We conclude that factors related to lower limb TcPO2 vary depending on measurement site. Autonomic neuropathy is not an important determinant of TcPO2 in the feet of diabetic subjects. Although several predictors of TcPO2 were identified, most of the variance of this measurement remains unexplained.

Objective: To determine the extent of functional impairment among veterans with diabetes and investigate whether such functional impairment is associated with measures of glycemic control, sensory neuropathy, lower extremity macrovascular disease, or other comorbid conditions., Research Design and Methods: A 20-item general health survey (SF-20) developed by the Medical Outcomes Study (MOS) Group, was administered to 577 subjects participating in a prospective study of risk factors for diabetic foot ulceration. Measures of glycemic control and neurovascular disease included GHb, sensory lower extremity neuropathy assessed by aesthesiometry, and segmental lower extremity doppler blood pressures., Results: Veterans with diabetes have major decreases in all domains of functional status; 87% were in poor health in terms of physical functioning and 86% in terms of health perceptions. Those with advancing age, symptoms of neuropathy and claudication, and a medical history of complications associated with diabetes had significantly more impairment of health status than those without. GHb values did not correlate with functional status measures. Subjects with neuropathy had statistically significant functional impairment. Subjects with vasculopathy had only two significantly low health status measures., Conclusions: In summary, the findings from this survey reveal that veterans with diabetes have low functional status scores. The presence of symptoms and complications accounts for only part of the impairments experienced by this group.

Objective: To explore the associations between blood pressure and both fasting insulin and C-peptide levels., Research Design and Methods: A cross-sectional analysis was conducted of 895 normoglycemic members of a bi-ethnic community in Colorado who were selected from a control group recruited for a geographically based study of diabetes mellitus prevalence and risk factors. All subjects included in this study had normal glucose tolerance as judged by a 75-g oral glucose tolerance test interpreted using World Health Organization criteria. None of the subjects were taking antihypertensive medication. Multiple linear regression analysis was used to examine relationships between fasting insulin and C-peptide levels and blood pressure., Results: Among all subjects, diastolic blood pressure was found to significantly increase with increasing levels of both hormones (insulin coefficient = 0.197, P = 0.013; C-peptide coefficient = 0.0436, P = 0.004), whereas systolic blood pressure was significantly related to fasting C-peptide level (coefficient = 0.0295, P = 0.050). These relationships were similar in magnitude for both Hispanic and non-Hispanic white subjects, but were diminished among women and subjects with a higher body mass index., Conclusions: Higher fasting insulin and C-peptide levels are associated with higher blood pressure, but these relationships are modified by sex and degree of obesity.

Objective: To estimate the prevalence of diabetes mellitus and overweight in two populations of Alaska Natives and to compare the results with previous data., Research Design and Methods: Participants' heights, weights, and random plasma glucose levels were determined. Those with a glucose of greater than or equal to 6.72 mM received a follow-up glucose-tolerance test, interpreted by WHO criteria. Overweight was defined by National Center for Health Statistics criteria and also by criteria used in previous studies. The subjects were Eskimo and Athabascan residents greater than or equal to 40 yr of age in 15 villages in southwestern Alaska., Results: Diabetes prevalence was 4.7% for Eskimos and 10.0% for Indians. Among Eskimo men and women, the prevalence of overweight was 34 and 56%, respectively, among Indian men and women, it was 29 and 55%, respectively. Comparisons with past data indicate that the prevalence of diabetes has increased from 1.7% in 1962 for Eskimos and 1.8% in 1969 for Indians., Conclusions: The prevalence of diabetes appears to have increased among Eskimos and Indians in Alaska. Overweight appears to be a significant problem in both groups.

The natural history of tissue repair and the critical determinants of faulty healing of diabetic ulcers remain obscure despite recent advances in our knowledge of the cellular physiology of normal cutaneous healing. To characterize the chronology and identify important factors affecting healing, we applied an objective method to quantify the rate of wound healing of full-thickness lower-extremity ulcers in 46 diabetic outpatients who received local wound care under a standardized clinical protocol. The initial ulcer healing rate, eventual status of tissue repair, and definitive clinical outcome were not significantly associated with age; diabetes type, duration, or treatment; level or change in glycosylated hemoglobin; current smoking; presence of sensory neuropathy; ulcer location or class; initial infection; or frequency of recurrent infections. However, direct measures of local cutaneous perfusion, estimated by periwound measurements of transcutaneous O2 tension (TcPo2) and transcutaneous CO2 tension (TcPco2), were significantly associated with the initial rate of tissue repair (P = 0.003 and 0.005, respectively). The strong prediction of early healing by these parameters of local skin perfusion was independent from the effects of segmental Doppler arterial blood pressure at the dorsalis pedis, although eventual ulcer reepithelialization was significantly related to foot blood pressure and periwound TcPo2 and TcPco2. We conclude that periwound cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing, indicating a 39-fold increased risk of early healing failure when the average periwound TcPo2 is less than 20 mmHg.

The prevalence of diabetes mellitus in Alaska Natives has been thought to be low, but no survey of this condition in all natives has been conducted. Medical records from 1979 to 1985 were reviewed to determine the prevalence of diagnosed diabetes mellitus in Alaska Natives. Computerized outpatient and inpatient medical record data and clinician reports were used to identify cases. As of December 1985, 610 living Alaska Natives fulfilled diagnostic criteria for diabetes. Type II diabetes mellitus was found in 564 subjects, type I diabetes was found in 15 subjects, and unspecified type of diabetes was found in 31 subjects. The overall age-adjusted prevalence of diabetes mellitus, 15.7/1000, was lower than the overall United States rate of 24.7/1000. However, age-adjusted prevalence varied considerably by ethnic group; the prevalence was 27.2/1000 among Aleuts, 22.0/1000 among Alaskan Indians, and 8.8/1000 among Alaskan Eskimos. Rates within the Eskimo subgroups varied by a factor of four. Compared with previous reports, the prevalence of diabetes mellitus in Alaskan Eskimos appears to have increased. Diabetes mellitus is no longer a rare condition among Alaska Natives.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients. [ABSTRACT FROM AUTHOR]