bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Semmes-Weinstein monofilament in the strong heart study. Risk factors for clinical neuropathy.
Authors: Sosenko J M , Sparling Y H , Hu D , Welty T , Howard B V , Lee E , Robbins D C
Published: March 2007

OBJECTIVE: We used the Semmes-Weinstein 5.07 monofilament to assess the prevalence of foot insensitivity and its relationship to potential risk factors. RESEARCH DESIGN AND METHODS: There were 3,638 American Indian participants from Arizona, North and South Dakota, and Oklahoma who attended a study clinic on two occasions: baseline and follow-up, 4 years later. Oral glucose tolerance tests were performed at the visits for those who had not previously been diagnosed as having diabetes. A total of 2,051 participants were diagnosed with diabetes before the study or at the subsequent study visits. At the follow-up visit, participants were tested for their ability to sense the 5.07 (10 g) monofilament at 10 sites of the foot. The prevalence of foot insensitivity was ascertained, and its relation to characteristics of participants was assessed in both univariate and logistic regression analyses. RESULTS: Diabetic participants had a much higher prevalence of foot insensitivity (defined as greater than or equal to five incorrect responses) than nondiabetic participants (14 vs. 5%, respectively). However, marked foot insensitivity was uncommon within the first few years of diagnosis of diabetes. Among the diabetic participants, those diagnosed before study entry had the highest prevalence of foot insensitivity. The prevalence of foot insensitivity was highest in the Arizona Indians (22 vs. 9% in the Dakotas and 8% in Oklahoma). In a logistic regression analysis, foot insensitivity was significantly and independently related to center (Arizona versus others), age, duration of diabetes, and height. CONCLUSIONS: Marked foot insensitivity is prevalent in the diabetic American Indian population, especially in Indians in Arizona; however, this insensitivity is apparently uncommon for several years after the diagnosis of diabetes. The data show that Indians with diabetes are particularly vulnerable to the risk of foot ulceration and that the diagnostic screening of diabetes may lead to better prevention of sensory neuropathy and subsequent foot ulceration.
Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes.
Authors: Couper J J , Taylor J , Fotheringham M J , Sawyer M
Published: March 2007

OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention. RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN). RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively). CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.
Discriminating glucose tolerance status by regions of interest of dual-energy X-ray absorptiometry. Clinical implications of body fat distribution.
Authors: Chang C J , Wu C H , Lu F H , Wu J S , Chiu N T , Yao W J
Published: March 2007

OBJECTIVE: To determine whether measuring body fat distribution by dual-energy X-ray absorptiometry (DEXA) can be used to discriminate glucose tolerance status. RESEARCH DESIGN AND METHODS: Using a 75-g oral glucose tolerance test, a total of 1,015 Chinese subjects (559 men and 456 women) were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes. Blood pressure and lipid profiles of these subjects were measured. Waist-to-hip ratio (WHR) and DEXA were used to evaluate the varying patterns of body fat distribution among the groups. RESULTS: Body fat distribution, as reflected by WHR and the centrality index, showed significant partial correlation coefficients with glycosylated hemoglobin, blood pressure, and lipid profiles in all subjects. After adjusting for age and BMI, there were significant differences among the three glycemic groups for all the cardiovascular risk factors except for total cholesterol level. The diabetic group had a significantly higher WHR and centrality index, but lower femoral fat percentage than the NGT and IGT groups. The diabetic group also showed higher abdominal fat percentage than the NGT group. Moreover, the IGT group had a higher centrality index than the NGT group. However, no significant differences were found in the percentage of lean tissue mass among the three groups. Using multiple stepwise logistic regression models, the centrality index remained a significant factor for discriminating different glucose tolerance status independent of the percentage total body fat. CONCLUSIONS: Central obesity has shown significant correlation with cardiovascular risk factors among the three different glycemic groups. Centrality index measured by DEXA appears to be the better predictor of glucose intolerance, compared with WHR, abdominal fat, and general obesity (reflected by percentage total body fat or BMI) in a large cohort of the Chinese population.
Eating habits, body weight, and insulin misuse. A longitudinal study of teenagers and young adults with type 1 diabetes.
Authors: Bryden K S , Neil A , Mayou R A , Peveler R C , Fairburn C G , Dunger D B
Published: March 2007

OBJECTIVE: To examine disordered eating, insulin misuse, weight change, and their relationships with glycemic control and diabetic complications in adolescents with type 1 diabetes followed up over eight years. RESEARCH DESIGN AND METHODS: Of 76 adolescents (43 male, 33 female) with type 1 diabetes aged 11-18 years at the first assessment, 65 were interviewed as young adults (aged 20-28 years). Eating habits were assessed using a standardized Eating Disorder Examination. Height and weight were determined and BMI calculated. Three consecutive urine specimens were collected for measurement of albumin/creatinine ratio and other significant diabetic complications were recorded. Glycemic control was assessed by glycated hemoglobin. RESULTS: Weight and BMI increased from adolescence to young adulthood. Females were overweight as adolescents and both sexes were overweight as young adults. Concern over weight and shape increased significantly for both sexes from adolescence to young adulthood. This increase in concern was reflected in increased levels of dietary restraint. Features of disordered eating were apparent in females at both assessments, but no patients met the criteria for anorexia nervosa or bulimia nervosa at either assessment. A total of 10 (30%) females, but none of the males admitted underusing insulin to control weight. Five (45%) females with microvascular complications had intentionally misused insulin to prevent weight gain. CONCLUSIONS: An increase in BMI from adolescence to adulthood was associated with higher levels of concern over shape and weight and more intense dietary restraint, especially among females. Overt eating disorders were no more prevalent in these patients than in the general population, but milder forms of disordered eating were common and had implications for diabetes management. Insulin omission for weight control was frequent among females and may contribute to poor glycemic control and to risk of complications.
Plantar pressures are elevated in the neuroischemic and the neuropathic diabetic foot.
Authors: Pitei D L , Lord M , Foster A , Wilson S , Watkins P J , Edmonds M E
Published: March 2007

OBJECTIVE: Clinical observation has noted that diabetic neuropathic ulcers occur frequently on the plantar surface, whereas neuroischemic ulcers seem to occur often on the foot margins. The reason for this difference in the site of ulceration is unknown, but it may be related to differences in pressure loading. The aim of the study was to compare vertical in-shoe foot pressures measured during walking (using the F-SCAN system) in four groups of patients whose degree of neuropathy was measured by vibration perception threshold (VPT). RESEARCH DESIGN AND METHODS: Subjects included 14 neuroischemic diabetic patients (VPT 29.3 +/- 13.5 V) with history of ulceration on the margins of the foot, 18 patients with neuropathy alone (VPT 38.7 +/- 12.7 V) and previous history of ulceration on the plantar surface, 10 diabetic control patients (VPT 9.9 +/- 2.7 V), and 15 nondiabetic control subjects (VPT 7.0 +/- 0.5 V). RESULTS: When compared with the other three groups, neuroischemic patients had higher foot pressures when measured as mean peak pressures and highest peak pressures under four areas of the foot: medial and lateral forefoot, hallux, and heel. Furthermore, when measuring the maximum pressures developed at any point under the plantar surface, the neuroischemic patients also had the most elevated pressures (757.6 +/- 135.9 kPa), significantly higher than those found in the neuropathic group (482.8 +/- 68.6 kPa, P = 0.04) and in both diabetic control patients (310.2 +/- 34.7 kPa, P = 0.008) and nondiabetic controls subjects (365.1 +/- 49.8 kPa, P = 0.007). CONCLUSIONS: Despite having increased plantar pressures and a comparable degree of neuropatny, the neuroischemic patients did not have a history of ulceration on the plantar surface. These observations may have relevance to different mechanisms of ulcer formation in the neuroischemic and neuropathic foot.
Education and the metabolic syndrome in women.
Authors: Wamala S P , Lynch J , Horsten M , Mittleman M A , Schenck-Gustafsson K , Orth-Gomér K
Published: March 2007

OBJECTIVE: The main objective was to examine the association between the metabolic syndrome and socioeconomic position (as indicated by education) among women. RESEARCH DESIGN AND METHODS: The study sample comprised healthy women (aged 30-65 years) in Sweden who were representative of the general population in a metropolitan area. Socioeconomic position was measured by educational level (mandatory [< or = 9 years], high school, or college/university). The metabolic syndrome was defined as the presence of two or more of the following components: 1) fasting plasma glucose level > or = 7.0 mmol/l; 2) arterial blood pressure > or = 160/90 mmHg; 3) fasting plasma triglycerides > or = 1.7 mmol/l and/or HDL cholesterol < 1.0 mmol/l; and 4) central obesity (waist-to-hip ratio > 0.85 and/or BMI > 30 kg/m2). RESULTS: After adjustment for age, the risk ratio for the presence of the metabolic syndrome comparing the lowest (< or = 9 years) with the highest (college/university) education was 2.7 (95% CI 1.1-6.8). This association persisted after controlling for menopausal status, family history of diabetes, and behavioral risk factors. CONCLUSIONS: Low education is associated with increased risk for metabolic syndrome in middle-aged women. These findings show that not only are women with low socioeconomic position at increased risk for individual risk factors that are associated with cardiovascular disease and type 2 diabetes, they are also at increased risk for the metabolic clustering of risk factors.
Risk and protective factors associated with screening for complications of diabetes in a health maintenance organization setting.
Authors: Simon L P , Albright A , Belman M J , Tom E , Rideout J A
Published: March 2007

OBJECTIVE: To identify risk and protective factors associated with screening for complications of diabetes, we performed a cross-sectional study of 3,612 diabetic members enrolled in CaliforniaCare, a large network-model health maintenance organization (HMO). RESEARCH DESIGN AND METHODS: We used the Health Plan and Employer Data Information Set (HEDIS) 3.0 technical definition to identify all members (aged > or = 31 years) receiving any diabetes medication(s) during a 12-month period. Using a telephone survey instrument, identified members were interviewed about their diabetes care and screening, patient, and provider history. Survey data were supplemented with HMO claims and demographic information. Multivariate analysis was performed to identify demographic, clinical, and utilization characteristics that affect the odds of diabetic members receiving annual retinal examination, foot examination, and HbA1c testing. RESULTS: While results varied by screening category, the odds of obtaining screening were higher for diabetic members who were older, spoke English, received diabetes nutrition counseling, visited a diabetes specialist physician, belonged to a diabetes association or support group, used insulin, performed glycemic level self-examination at least once a day, and had higher overall prescription drug use (suggesting higher comorbidity). Since this study is a cross-sectional review, these results do not imply a cause-and-effect relationship between dependent and independent variables. CONCLUSIONS: Results of this study suggest barriers, risks, and protective factors associated with screening for complications of diabetes. Diabetic members who do not possess these characteristics may be at increased risk.
Fasting proinsulin concentrations predict the development of type 2 diabetes.
Authors: Wareham N J , Byrne C D , Williams R , Day N E , Hales C N
Published: March 2007

OBJECTIVE: The development of specific assays allows the different molecules in the proinsulin processing pathway to be measured separately. 32,33 Split proinsulin is the predominant form of proinsulin and accounts for the disproportionate hyperproinsulinemia seen in individuals with prevalent type 2 diabetes. This study was established to examine whether the concentration of this molecule predicts diabetes. RESEARCH DESIGN AND METHODS: A population-based longitudinal cohort study was conducted in Ely, Cambridgeshire. At baseline, 1,122 individuals completed a 75-g oral glucose tolerance test (OGTT). At the 4.5-year follow-up study, repeat OGTTs were performed on 937 of the cohort of 1,071 individuals who had been nondiabetic at baseline. RESULTS: A total of 26 people progressed to diabetes as determined by the OGTTs. The risk of progression was strongly related to the fasting glucose concentration (relative risk [RR] comparing top with bottom quartile 17.6 [95% CI 2.4-130.4]) and fasting 32,33 split proinsulin (RR 16.4 [2.2-121.9]), but less strongly to the fasting insulin (RR 4.41 [1.5-12.9]) or intact proinsulin (RR 5.2 [1.5-17.3]). In multivariate analyses, these associations were independent of age, sex, BMI, and baseline glucose tolerance category. Subjects in the top quartile for fasting glucose and total proinsulin with a family history of diabetes were a high-risk subgroup (incidence 65.8 per 1,000 person-years of follow-up [pyfu]); 30% of them progressed to diabetes at follow-up. CONCLUSIONS: Fasting 32,33 split proinsulin independently predicts the development of diabetes. This prediction was better than that observed for either the insulin or intact proinsulin concentrations. The combination of family history, fasting glucose, and total proinsulin identified a subgroup of individuals at high risk of progression who might benefit from targeted interventions.
Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes.
Authors: Kelly I E , Han T S , Walsh K , Lean M E
Published: March 2007

OBJECTIVE: To examine the effects of a thiazolidinedione (600 mg troglitazone) insulin-sensitizing treatment on total body fat measured by underwater weighing, on intra- and extra-abdominal fat mass using magnetic resonance imaging (MRI), and on anthropometric measures. RESEARCH DESIGN AND METHODS: Type 2 diabetic outpatients were studied in a double-blind randomized trial carried out at Glasgow Royal Infirmary, Scotland. RESULTS: Groups who received troglitazone (8 men, 3 women) and placebo (8 men, 2 women) were well matched for age, BMI, total body fat percentage by underwater weighing, and intra-abdominal fat (kilograms) by MRI. After 12 weeks, body weight changes in the troglitazone group (mean +0.66 kg [95% CI -0.71 to 2.04], P = 0.31) and the placebo group (mean +0.25 kg [-0.64 to 1.13], P = 0.55) were not statistically different. Changes in total body fat with troglitazone (mean +1.02% body wt [-1.13 to 3.17], P = 0.32) and placebo (mean -0.54% body wt [-1.68 to 0.59], P = 0.31) were not significantly different. There was, however, a decrease in intra-abdominal fat mass in the troglitazone-treated group (mean -0.47 kg [-0.79 to -0.13], P = 0.01), and this was significantly different (P = 0.03) from placebo treatment (mean -0.41 kg [-0.77 to -0.05]). CONCLUSIONS: Treatment with the thiazolidinedione troglitazone in human patients with type 2 diabetes decreases intra-abdominal fat mass but does not affect total body fat or weight. This potentially valuable effect points to a differential action on insulin sensitivity in different adipose tissue depots.
Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius?
Authors: Shaw J E , Zimmet P Z , de Courten M , Dowse G K , Chitson P , Gareeboo H , Hemraj F , Fareed D , Tuomilehto J , Alberti K G
Published: March 2007

OBJECTIVE: To determine if impaired fasting glucose (IFG; fasting plasma glucose level 6.1-6.9 mmol/l) can predict future type 2 diabetes as accurately as does impaired glucose tolerance (IGT; 2-h plasma glucose level 7.8-11.0 mmol/l). RESEARCH DESIGN AND METHODS: A longitudinal population-based study was performed with surveys in 1987 and 1992 on the island of Mauritius, assessing diabetes status by the oral glucose tolerance test. A total of 3,717 subjects took part in both surveys. Of these subjects, 3,229 were not diabetic in 1987 and formed the basis of this study. RESULTS: At baseline, there were 607 subjects with IGT and 266 subjects with IFG. There were 297 subjects who developed diabetes by 1992. For predicting progression to type 2 diabetes, the sensitivity, specificity, and positive predictive values were 26, 94, and 29% for IFG and 50, 84, and 24% for IGT, respectively. Only 26% of subjects that progressed to type 2 diabetes were predicted by their IFG values, but a further 35% could be identified by also considering IGT. The sensitivities were 24% for IFG and 37% for IGT in men and 26% for IFG and 66% for IGT in women, respectively. CONCLUSIONS: These data demonstrate the higher sensitivity of IGT over IFG for predicting progression to type 2 diabetes. Screening by the criteria for IFG alone would identify fewer people who subsequently progress to type 2 diabetes than would the oral glucose tolerance test.
Prevalence and correlates of the insulin resistance syndrome among Native Americans. The Inter-Tribal Heart Project.
Authors: Greenlund K J , Valdèz R , Casper M L , Rith-Najarian S , Croft J B
Published: March 2007

OBJECTIVE: The clustering of factors characterizing the insulin resistance syndrome has not been assessed among Native Americans, a population at high risk for diabetes and cardiovascular disease. We examined the distribution and correlates of the insulin resistance syndrome among individuals in three Chippewa and Menominee communities in Wisconsin and Minnesota. RESEARCH DESIGN AND METHODS: Cross-sectional data from 488 men and 822 women ages > or = 25 years in the Inter-Tribal Heart Project (1992-1994) were included. The clustering of each individual trait (hypertension, diabetes, high triglycerides, and low HDL cholesterol) with the other traits and the association of the number of traits with measures of adiposity and insulin levels were examined. RESULTS: Among the men, 40.4, 32.6, 17.4, and 9.6% had none, one, two, or at least three of the four traits, respectively; among the women, the respective percentages were 53.2, 25.6, 15.3, and 6.0%. The percentage of individuals with each particular trait significantly increased (P < 0.01) among those with none, one, or at least two other syndrome traits. Having more syndrome traits was significantly related (P < 0.001) to higher BMI, conicity index, waist circumference, and waist-to-hip and waist-to-thigh ratios. Among individuals with normal glucose levels, having more syndrome traits was significantly related (P < or = 0.05) to higher fasting insulin levels after adjusting for age and measures of adiposity, although associations were attenuated with adjustment for either BMI or waist circumference. CONCLUSIONS: Traits characterizing the insulin resistance syndrome were found to be clustered to a significant degree among Native Americans in this study. Comprehensive public health efforts are needed to reduce adverse levels of these risk factors in this high-risk population.
Persistence of depressive symptoms in diabetic adults.
Authors: Peyrot M , Rubin R R
Published: March 2007

OBJECTIVE: To determine the level and pattern of persistent depressive symptoms among adults with diabetes and identify factors associated with increased risk of being persistently depressed. RESEARCH DESIGN AND METHODS: A self-report depression symptom inventory was administered to 245 patients at two initial time points--the beginning and end of a comprehensive outpatient diabetes education program--and at 6-month follow-up. RESULTS: Only 13% of subjects were persistently depressed (i.e., exceeded the criterion for depression symptoms at all three time points). The rate of being depressed at follow-up was 10% for those negative for depression symptoms at either of the initial time points, 36% for those positive at one initial time point, and 73% for those positive at both initial time points (P < 0.0001). Those at increased risk for being persistently depressed were those who did not graduate from high school, had more than two complications of diabetes, and were not treated with insulin. CONCLUSIONS: Persistent depressive symptomatology is present in a substantial number of diabetic adults and can be effectively predicted using simple screening instruments during initial contacts. Risk factors for being persistently depressed only partly overlap those for transient depressive symptoms and represent a possible biological dimension.
Long-term intensive treatment of type 1 diabetes with the short-acting insulin analog lispro in variable combination with NPH insulin at mealtime.
Authors: Lalli C , Ciofetta M , Del Sindaco P , Torlone E , Pampanelli S , Compagnucci P , Cartechini M G , Bartocci L , Brunetti P , Bolli G B
Published: March 2007

OBJECTIVE: To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes, and if so, what its effects are on glycemic control and frequency and awareness of hypoglycemia. RESEARCH DESIGN AND METHODS: We randomized 56 type 1 diabetic patients to treatment with either lispro (n = 28) or human regular insulin (Hum-R; n = 28) as mealtime insulin for 1 year (open design, parallel groups). Lispro was injected at mealtime and Hum-R was given 10-40 min before meals (bedtime NPH was continued on both occasions). With lispro, NPH was added at breakfast (approximately 70/30), lunch (approximately 60/40), and supper (approximately 80/20) (mixing percentage of lispro/NPH) to optimize premeal and bedtime blood glucose. RESULTS: Total daily insulin units were no different in the two treatment groups, but with lispro approximately 30% less short-acting insulin at meals and approximately 30% more NPH was needed versus Hum-R (P < 0.05). The bedtime NPH dosage was no different. With lispro + NPH, the mean daily blood glucose was lower than with Hum-R (8.0 +/- 0.1 vs. 8.8 +/- 0.1 mmol/l; P < 0.05), HbA1c was lower (6.34 +/- 0.10 vs. 6.71 +/- 0.11%, mean value over 1 year; P < 0.002), and hypoglycemia (blood glucose < or = 3.8 mmol/l) was less frequent (7.4 +/- 0.5 vs. 11.5 +/- 0.7 episodes/patient-month) and tended to occur more within 90 min after meals than in the postabsorptive state (P < 0.05 vs. Hum-R). After 1 year, plasma adrenaline and symptom responses to experimental, stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude (P < 0.05). CONCLUSIONS: We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term. Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia.
Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group.
Authors: Schultz C J , Konopelska-Bahu T , Dalton R N , Carroll T A , Stratton I , Gale E A , Neil A , Dunger D B
Published: March 2007

OBJECTIVE: The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years. RESULTS: MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes. CONCLUSIONS: Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk.
Natural history of diabetic gastroparesis.
Authors: Kong M F , Horowitz M , Jones K L , Wishart J M , Harding P E
Published: March 2007

OBJECTIVE: The major aim of this study was to evaluate the prognosis of diabetic gastroparesis. RESEARCH DESIGN AND METHODS: Between 1984 and 1989, 86 outpatients with diabetes (66 type 1, 20 type 2; 40 male, 46 female) underwent assessment of solid and liquid gastric emptying and esophageal transit (by scintigraphy), gastrointestinal symptoms (by questionnaire), autonomic nerve function (by cardiovascular reflex tests), and glycemic control (by HbAlc and blood glucose concentrations during gastric emptying measurement). These patients were followed up in 1998. RESULTS: Of the 86 patients, solid gastric emptying (percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients. At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up. In the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups. Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were alive. After adjustment for the effects of other factors that showed a relationship with the risk of dying, there was no significant relationship between either gastric emptying or esophageal transit and death. CONCLUSIONS: In this relatively large cohort of outpatients with diabetes, there was no evidence that gastroparesis was associated with a poor prognosis.
Impact of the work environment on glycemic control and adaptation to diabetes.
Authors: Trief P M , Aquilino C , Paradies K , Weinstock R S
Published: March 2007

OBJECTIVE: To evaluate quantitatively whether the work environments of adults with diabetes relate to the adequacy of metabolic control and/or to the individual's adaptation to diabetes and to explore qualitatively the interactions between an individual's life at work and ways of coping with diabetes. RESEARCH DESIGN AND METHODS: A total of 129 insulin-requiring adults who were employed outside of the home were assessed on a single occasion. They completed two work system measures (The Work Environment Scale and The Work Apgar Scale) and two quality-of-life measures (The Diabetes Quality of Life Scale and The Appraisal of Diabetes Scale). Subjects also participated in a semi-structured interview concerning the interaction of work and diabetes. Glycemic control was assessed by using HbAlc results. Demographic data (age, sex, diabetes type, duration of diabetes, number of diabetes-related medical complications) were gathered from the charts. RESULTS: Concerning glycemic control, neither of the work system measures was a significant predictor of HbAlc. Concerning psychosocial adaptation, supervisor support was found to be a significant predictor of positive appraisal and diabetes-related satisfaction. Involvement and coworker cohesion also predicted aspects of diabetes-related quality of life. Interview themes showed that for a minority (18%), diabetes affected choice of work and that for a majority (60%), diabetes affected relationships at work and raised financial/job concerns (49%). Most adjust their diet, blood glucose testing, and exercise regimen through work-related modifications. CONCLUSIONS: For insulin-treated adults with diabetes, work system variables do not directly relate to glycemic control, but they do relate to psychosocial adaptation. Future work should examine further the specific aspects of the workplace that might affect adaptation, with the goal being to develop worksite interventions that target not only the employee with diabetes but also their supervisors and coworkers.
Intact proinsulin and beta-cell function in lean and obese subjects with and without type 2 diabetes.
Authors: Røder M E , Dinesen B , Hartling S G , Houssa P , Vestergaard H , Sodoyez-Goffaux F , Binder C
Published: March 2007

OBJECTIVE: Type 2 diabetes is a heterogeneous disease in which both beta-cell dysfunction and insulin resistance are pathogenetic factors. Disproportionate hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type 2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or insulin resistance may result in secretion of immature beta-cell granules with a higher content of intact proinsulin. RESEARCH DESIGN AND METHODS: We investigated the impact of obesity on beta-cell secretion in normal subjects and in type 2 diabetic patients by measuring intact proinsulin, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects. RESULTS: Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4 vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon stimulation, PIM levels were disproportionately elevated (PIM/intact insulin based on area under the curve analysis) in diabetic patients (LD vs. LC and OD vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P < 0.05. Intact insulin and C-peptide net responses were significantly reduced in type 2 diabetic patients, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/- 3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05. CONCLUSIONS: Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.
Relationship between glomerular hyperfiltration and ACE insertion/deletion polymorphism in type 1 diabetic children and adolescents.
Authors: Bouhanick B , Gallois Y , Hadjadj S , Boux de Casson F , Limal J M , Marre M
Published: March 2007

OBJECTIVE: Glomerular hyperfiltration may predict diabetic nephropathy in type 1 diabetes, and some studies suggest that the ACE D allele is associated with diabetic nephropathy. The aim of this study was to examine a possible relationship between glomerular hyperfiltration and ACE insertion/deletion (I/D) polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted to examine the relationship between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1 diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA1c 9.5 +/- 1.9%). Glomerular hyperfiltration (defined as a glomerular filtration rate [GFR] > or = 135 ml.min-1. 1.73 m-2 and by 51Cr-labeled EDTA plasma disappearance technique) and ACE I/D genotypes and plasma levels (enzyme-linked immunosorbent assay [ELISA] method) were determined. RESULTS: Of the patients, 29 (38%) displayed glomerular hyperfiltration. An association between glomerular hyperfiltration and ACE (I/D) polymorphism was observed (chi 2 = 7.09, P = 0.029) because of a reduced proportion of DD genotypes among patients with glomerular hyperfiltration (4 vs. 19; chi 2 = 6.03, P = 0.014) and not because of an excess of the II genotype (5 vs. 9; chi 2 = 0.04, P = 0.83). Age, diabetes duration, age at diabetes onset, and HbA1c were not different according to genotype. Patients with glomerular hyperfiltration had low plasma ACE levels, compared with those with normal glomerular filtration (457 +/- 157 vs. 553 +/- 186 micrograms/l; P = 0.027). CONCLUSIONS: These results suggest an unexpected association between glomerular hyperfiltration and ACE (I/D) polymorphism, characterized by a defect of the DD genotype among type 1 diabetic children and adolescents with glomerular hyperfiltration.
Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application.
Authors: Wagner A , Risse A , Brill H L , Wienhausen-Wilke V , Rottmann M , Sondern K , Angelkort B
Published: March 2007

OBJECTIVE: Despite modern concepts in therapy by low-dose insulin application and better care in intensive care units (ICUs), there still is a mortality of 5-10% for severe diabetic ketoacidosis (DKA). The aim of this study was to develop a therapy concept to reduce complications and mortality in DKA. RESEARCH DESIGN AND METHODS: From 1986 to 1997, 114 consecutive patients (mean [range]; age 34 [11-74] years) with type 1 diabetes suffering from severe DKA were treated on ICUs and investigated in a retrospective and prospective study. The following are the criteria for admission onto ICUs: < 7.20 pH level, > 300 mg/dl blood glucose, less than -12 mmol/l base excess, or < 300 mg/dl blood glucose plus severe symptoms (i.e., coma). We treated patients according to the following concepts: very-low-dose insulin application by a basal insulin infusion of 1 U/h (0.5-4.0 U/h i.v.), maximal decrease of blood glucose level by 50 mg. dl-1. h-1, slow-motion reequilibration by fluid substitution of 1,000 ml/h (Ringer-Lactate, NaCl 0.9% or half-electrolyte fluids) in the first 4 h, potassium replacement and heparin (500-1,000 U/h i.v.). RESULTS: When patients were admitted to ICU, we found the following parameters: mean (range); 609.0 (86.0-1,428.0) mg/dl blood glucose level; 7.13 (6.53-7.36) pH level; and -19.7 (-41.2 to -7.0) mmol/l base excess. After 12 h of treatment, we reached the following parameters: mean values; 251 mg/dl blood glucose level, 7.31 pH level, and -9.37 mmol/l base excess level. All patients survived without any lasting deficiencies or fatal complications. CONCLUSIONS: Very-low-dose insulin application and slow-motion reequilibration plus monitored substitution of electrolytes are the basic strategies in the treatment of severe DKA. In our view, small doses of infused insulin are the main reason for the safe results of this therapy program.
Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.
Authors: Smith N L , Heckbert S R , Bittner V A , Savage P J , Barzilay J I , Dobs A S , Psaty B M
Published: March 2007

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort. RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes. RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997. CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.
Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.
Authors: Ciofetta M , Lalli C , Del Sindaco P , Torlone E , Pampanelli S , Mauro L , Chiara D L , Brunetti P , Bolli G B
Published: March 2007

OBJECTIVE: To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied. RESULTS: The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05), but not in group 3 (NS) vs. group 1.
Improved postprandial glycemic control with insulin aspart. A randomized double-blind cross-over trial in type 1 diabetes.
Authors: Lindholm A , McEwen J , Riis A P
Published: March 2007

OBJECTIVE: Insulin aspart is a novel rapid-acting insulin analog. This study was performed to compare the postprandial serum glucose control after administration of insulin aspart with that of unmodified human insulin. RESEARCH DESIGN AND METHODS: The trial was a double-blind double-dummy injection three-way cross-over study in 22 subjects with type 1 diabetes. Insulin aspart was injected subcutaneously immediately before the meal, and human insulin was injected subcutaneously 30 min before the meal or immediately before the meal. RESULTS: The postprandial glucose control as assessed by the excursion of serum glucose was superior with insulin aspart as compared with that with human insulin injected immediately before or 30 min before a meal (891 +/- 521 vs. 1,311 +/- 512 vs. 1,106 +/- 571 mmol.l-1.min-1, P < 0.0001 and P < 0.02). This was accompanied by a significantly lower glucose maximum concentration [Cmax(SG)] for insulin aspart than for human insulin injected immediately before the meal (13.5 +/- 3.5 vs. 16.4 +/- 3.4 mmol/l, P < 0.001). Insulin aspart was, on average, absorbed twice as fast as human insulin, with median time to insulin aspart Cmax(ins) on the order of 40 min, and the maximum concentration was approximately twice as high for insulin aspart. The relative bioavailability of the insulins indicated a similar extent of absorption. Insulin aspart was well tolerated. CONCLUSIONS: This study demonstrates the ability of insulin aspart to improve postprandial glucose control when compared with human insulin.
Impact of peripheral neuropathy on bone density in patients with type 1 diabetes.
Authors: Rix M , Andreassen H , Eskildsen P
Published: March 2007

OBJECTIVE: To investigate whether peripheral neuropathy (PN), as part of the microangiopathic complex, affects bone mineral density (BMD) of the peripheral or the axial skeleton in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Three study groups were examined. Group 1 comprised 21 males with type 1 diabetes and severe PN with a mean (range) duration of diabetes of 28 (9-59) years and an HbA1c of 8.2% (6.3-10.4). Group 2 comprised 21 male type 1 diabetic patients with absent or mild PN matched to patients of group 1 regarding age, weight, and duration of diabetes. Group 3 comprised 21 control subjects. BMD was measured by dual-energy x-ray absorptiometry (DEXA) and by quantitative ultrasound of the calcaneus. PN was determined by biothesiometry. Levels of physical activity were assessed through guided questionnaires. RESULTS: In group 1, BMD was significantly reduced at all measured sites, compared with an expected Z score of 0 (spine, -1.01 +/- 0.34; femur, -0.94 +/- 0.25; forearm, -1.10 +/- 0.36). To a lesser extent, but still significantly, group 2 also showed reduced BMD values (spine, -0.60 +/- 0.26; femur, -0.55 +/- 0.25; forearm, -1.05 +/- 0.36), whereas group 3 had normal BMD values (-0.23 +/- 0.25, -0.10 +/- 0.21, -0.07 +/- 0.25, respectively). Group 1 had lower mean BMD levels than group 2 and group 3 at all measured sites, but a significant difference was found only between groups 1 and 3 at the site of the femur (analysis of variance, P < 0.05). Broadband ultrasound attenuation (BUA) of the calcaneus was significantly reduced in group 1 compared with groups 2 and 3 (108 +/- 3 vs. 115 +/- 2 and 115 +/- 2). Significant correlations between all DEXA measurements and BUA were demonstrated in both groups 1 and 2 (r values between 0.54 and 0.75). No significant differences in physical activity levels or body composition were demonstrated between the two patient groups. CONCLUSIONS: The present results suggest that in patients with type 1 diabetes, PN may be an independent risk factor for reduced BMD in the affected limbs as well as in the skeleton in general.