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PubMedDate not supplied

Diabetes Nutrition and Complications Trial: adherence to the ADA nutritional recommendations, targets of metabolic control, and onset of diabetes complications. A 7-year, prospective, population-based, observational multicenter study.

OBJECTIVE: To know the adherence to the ADA nutritional recommendations and its relation to targets of metabolic control and onset of diabetic complications in a sample of diabetic people in Spain. RESEARCH DESIGN AND METHODS: The Diabetes Nutrition and Complications Trial (DNCT) is a prospective, population-based, observational multicenter study designed to know the nutritional pattern, based on the 7-day food diaries, of a population with long-standing diabetes mellitus (93/99 type 1/type 2 diabetic patients, 20/18 years of duration of diabetes, and 6.9%/6.4% HbA(1c) values) and its relation with the onset of microvascular and macrovascular diabetes complications between 1993 and 2000. RESULTS: After a median follow-up period of 6.5 years, more than 55% of diabetic people complied with the recommendation of protein intake between 15% and 20%, but only 27% consumed less than 10% of saturated fatty acids (SFAs), the 13% achieved up 10% of polyunsaturated fatty acids (PUFAs) intake, the 39% consumed more than 60% from carbohydrate and monounsaturated fatty acids (MUFAs), and the 30% consumed <300 mg/day of cholesterol. In spite of these, more than 90% had an optimal HDL cholesterol and non-HDL cholesterol level, and triglycerides level, while less than 41% of diabetic people had an HbA(1c) value >7.5%. Moreover, more than 69% consumed a MUFAs-to-SFAs ratio >1.5 and the 46% a PUFAs-to-SFAs ratio >0.4. Nonadherence to nutritional recommendation, but MUFAs/SFAs ratio >1.5 and PUFAs/SFAs ratio >0.4, was associated with a reduction between 3.4- and 8.2-fold in the risk of onset of diabetic complications. CONCLUSIONS: The adherence to ADA nutritional recommendations for people with diabetes in Spain is rather poor except for the protein consumption. Only PUFAs/SFAs >0.4 and MUFAs/SFAs>1.5 were associated to near-optimal targets of metabolic control and a reduction in the risk of the onset of diabetic complications. These data suggest that other nutritional recommendations should be taken in mind.

Adult↗

PubMed1996

Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy.

BACKGROUND: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics. METHODS: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories. FINDINGS: 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001). INTERPRETATION: We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Acenocoumarol↗

PubMed1998

Minimizing complications of ultrasound-assisted lipoplasty: an initial experience with no related complications.

Numerous complications and increased operating times were reported with ultrasonically assisted lipoplasty in the first several months after introduction of the technology in the United States. The purpose of this study was to review early reported complications and management regimens, evaluate possible causes of problems, and apply indications and techniques to attempt to minimize complications during an initial experience with this technique beginning in January of 1997. Seven specific indications and modifications of existing techniques were developed and applied to an initial clinical series of 70 consecutive patients who underwent ultrasound-assisted suction lipoplasty between January 10, 1997, and August 1, 1997. Follow-up ranged from 1 to 7 months. No perioperative or postoperative complication occurred in any patient in this series. In this series of ultrasound-assisted lipoplasty cases, application of the following criteria resulted in a series of 70 patients with 1 to 7-month follow-up without complications: (1) selecting patients with well localized fat deposits who were no more than 20 percent above their ideal body weight; (2) infusing a solution of Ringer's Lactate containing 1 cc of 1:1000 epinephrine per 1000 cc into the area of fat removal, stopping infusion when the tissues first become firm, not infusing to marked tissue turgor or skin induration; (3) restricting the level of energy application to a minimum of 1 cm from the undersurface of the dermis; (4) limiting ultrasonic energy application in each area to approximately 1 minute per estimated 100 cc of total aspirate in a wet to superwet environment; (5) not performing ultrasound-assisted lipoplasty in the same area as another procedure that could potentially compromise tissue vascularity; (6) using a Lysonix 2000 generator and 5-mm golf tee tip probe at a power setting of 8 to apply ultrasonic energy to the area of fat removal, ceasing energy application when tissue resistance to the passage of the probe decreases and moving the cannula as rapidly as tissue resistance allows; and (7) using a standard elastic garment without adherent foam or other materials for 2 weeks postoperatively, encouraging all normal activity immediately, and restricting aerobic activities for 2 weeks.

Adolescent↗

PubMed1995

Multicentre study on prevalence of endocrine complications in thalassaemia major. Italian Working Group on Endocrine Complications in Non-endocrine Diseases.

OBJECTIVE: Thalassaemia major is a common and serious medical problem, worldwide. However, there are few data concerning the various endocrine disorders which occur in this condition. We have surveyed 25 Italian centres in order to establish the prevalences and times of onset of endocrine disorders in patients with beta-thalassaemia major. PROJECT AND PATIENTS: A questionnaire specifically designed to investigate the prevalences of endocrinopathies was sent to 25 paediatric and haematology departments. The following data were recorded in the questionnaire: sex, age, height and weight, pubertal status according to Tanner's classification, history of secondary amenorrhoea, type of endocrinopathy and hormone levels at diagnosis, associated complications, serum ferritin level, liver enzymes (ALT) and compliance with treatment. RESULTS: An analysis of data from 1861 patients showed that failure of puberty was the major clinical endocrine problem and was present in 51% of boys and 47% of girls, all over the age of 15 years. Secondary amenorrhoea was recorded in 23% of patients (mean age 18.3 years), primary hypothyroidism in 6.2% (mean age 15.8 years), insulin dependent diabetes mellitus in 4.9% (mean age 18.1 years) and hypoparathyroidism in 3.6% of the patients (mean age 18.7 years). At present, the majority are in the second or third decades of life. The prevalences of hypothyroidism, insulin dependent diabetes mellitus and hypoparathyroidism differed in the various centres, whereas the frequency of pubertal disorders was very similar. CONCLUSIONS: Our study has demonstrated several points. Endocrine evaluation in thalassaemic patients must be carried out regularly, especially in those patients over the age of 10 years with iron overload and poor compliance with chelation therapy. The prevalences of some complications, such as insulin dependent diabetes and hypothyroidism, were lower than previously recorded. Hence, it is to be hoped endocrine complications will be less common in the future, for patients who have started chelation therapy during the first years of life. Because of the improved survival of thalassaemic patients with insulin dependent diabetes, and the high incidence of multiple endocrine complications, it is important to carry out careful follow-up studies for the early detection of any other associated complications to facilitate correct treatment.

Adolescent↗

PubMed2003

Percutaneous dilatational tracheostomy in the ICU: optimal organization, low complication rates, and description of a new complication.

STUDY OBJECTIVES: To assess short-term and long-term complications of bronchoscopy-guided, percutaneous dilatational tracheostomy (PDT) and surgical tracheostomy (ST) and to report a complication of PDT that has not been described previously. DESIGN: Prospective survey. SETTING: University teaching hospital. PATIENTS: Two hundred eleven critically ill patients in our ICU. INTERVENTIONS: PDT was performed in 174 patients, under bronchoscopic guidance in most cases. ST was performed in 40 patients. RESULTS: No procedure-related fatalities occurred during PDT or ST. The incidence of significant complications (eg, procedure-related transfusion of fresh-frozen plasma, RBCs, or platelets, malpositioning or kinking of the tracheal cannula, deterioration of respiratory parameters lasting for > 36 h following the procedure, or stomal infection) in patients undergoing PDT was 4.0% overall and 3.0% when bronchoscopic guidance was used. No cases of paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, or clinically significant tracheal stenosis occurred in patients undergoing PDT. We attribute this low rate of complications to procedural and organizational factors such as bronchoscopic guidance, performance by or supervision of all PDTs by physicians with extensive experience in this procedure, and airway management by physicians who were well-versed in (difficult) airway management. In addition, an ear-nose-throat surgeon participated in the procedure in case conversion of the procedure to an ST should become necessary. We observed a complication that, to our knowledge, has not been reported previously. Five patients developed intermittent respiratory difficulties 2 to 21 days (mean, 8 days) after undergoing PDT. The cause turned out to be the periodic obstruction of the tracheal cannula by hematoma and the swelling of the posterior tracheal wall, which had been caused by intermittent pressure and chafing of the cannula on the tracheal wall. In between the episodes of obstruction, the cannula was open and functioning normally, which made the diagnosis difficult to establish. CONCLUSIONS: Bronchoscopy-assisted PDT is a safe and effective procedure when performed by a team of experienced physicians under controlled circumstances. The intermittent obstruction of the cannula caused by swelling and irritation of the posterior tracheal wall should be considered in patients who develop unexplained paroxysmal respiratory problems some time after undergoing PDT or ST.

Bronchoscopy↗

PubMed1999

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Adolescent↗

PubMed2005

Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes.

Several mechanistic pathways linking hyperglycemia to diabetes complications, including glycation of proteins and formation of advanced glycation end products (AGEs), have been proposed. We investigated the hypothesis that skin collagen glycation and AGEs predict the risk of progression of microvascular disease. We measured glycation products in the skin collagen of 211 Diabetes Control and Complications Trial (DCCT) volunteers in 1992 who continued to be followed in the Epidemiology of Diabetes Interventions and Complications study for 10 years. We determined whether the earlier measurements of glycated collagen and AGE levels correlated with the risk of progression of retinopathy and nephropathy from the end of the DCCT to 10 years later. In multivariate analyses, the combination of furosine (glycated collagen) and carboxymethyllysine (CML) predicted the progression of retinopathy (chi2 = 59.4, P < 0.0001) and nephropathy (chi2 = 18.2, P = 0.0001), even after adjustment for mean HbA(1c) (A1C) (chi2 = 32.7, P < 0.0001 for retinopathy) and (chi2 = 12.8, P = 0.0016 for nephropathy). The predictive effect of A1C vanished after adjustment for furosine and CML (chi2 = 0.0002, P = 0.987 for retinopathy and chi2 = 0.0002, P = 0.964 for nephropathy). Furosine explained more of the variation in the 10-year progression of retinopathy and nephropathy than did CML. These results strengthen the role of glycation of proteins and AGE formation in the pathogenesis of retinopathy and nephropathy. Glycation and subsequent AGE formation may explain the risk of these complications associated with prior A1C and provide a rational basis for the phenomenon of "metabolic memory" in the pathogenesis of these diabetes complications.

Adult↗

PubMed1995

The relationship between smoking and microvascular complications in the EURODIAB IDDM Complications Study.

OBJECTIVE: To examine the relationship between smoking and both glycemic control and microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: This was a prevalence survey of 3,250 men and women aged 15-60 years with IDDM from 31 diabetes centers in 16 European countries. Participants completed a questionnaire, had retinal photographs taken, and performed a 24-h urine collection. HbA1c, frequency of hypoglycemic and ketoacidotic episodes, urinary albumin excretion rates, and retinopathy were compared by smoking category. RESULTS: The prevalence of smoking was 35% in men and 29% in women. Current smokers had poorer glycemic control and, among men, were more likely to have had a ketoacidotic episode than were those who never smoked. Ex-smokers had equivalent glycemic control and marginally more hypoglycemic episodes did than those who never smoked. Current smokers had a higher prevalence of microalbuminuria and total retinopathy than did those who never smoked. Ex-smokers had a higher prevalence of macroalbuminuria and proliferative retinopathy than did those who never smoked, but both had a similar prevalence of microalbuminuria. Adjustment for either current or long-term glycemic control could not fully account for these differences. CONCLUSIONS: Smoking is associated with poorer glycemic control and an increased prevalence of microvascular complications compared with not smoking. Ex-smokers can achieve glycemic control equivalent to and have a prevalence of early complications similar to that of those who never smoked. We suggest that poorer glycemic control can account for some of the increased risk of complications in smokers, and that quitting smoking would be effective in reducing the incidence of complications. Urgent action is required to reduce the high smoking rates in people with IDDM.

Adolescent↗

PubMed1999

Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort.

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of > 1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro- and macrovascular outcomes. RESEARCH DESIGN AND METHODS: Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram. Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy. At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end. RESULTS: Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men). HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA1c difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA1c remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT. CONCLUSIONS: Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term follow-up in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications.

Adult↗

PubMed2001

[Complications in internal medicine. A study for clinical epidemiology and for prevention of medical complications in Swiss hospitals].

The committee of the heads of the swiss hospital departments of internal medicine are conducting a study for the prospective registration of complications of medical interventions in patients treated in hospitals. The objective is the reduction of complications by means of postgraduate and continuing education of the hospital staff and by organisational measures. The kind and number of all the interventions performed in each patient and the respective complications are registered by a means of multiple choice form. With this method the percentage of complications can be calculated for each kind of intervention and therefore is also a contribution to the clinical epidemiology of complications. The data are collected anonymously and regular feedback information on pertinent statistic and casuistic material from all the hospitals is provided to all the participants. The casuistic information is commented on by a group of experts. The results demonstrate that the study is well practicable and from 1998 to 2000 42,000 patients have been evaluated.

Education, Continuing↗

PubMed2005

[C-reactive protein in severe combined trauma not complicated and complicated by sepsis].

The role of C-reactive protein (CRP) was studied in the development of nonbacterial systemic inflammation response, infectious complications, severe sepsis in severe combined trauma. It was shown that daily quantitative indicators of CRP in blood of patients in the intensive care unit allowed prognosis of the development of nonbacterial systemic inflammation response, infectious complications and sepsis. The CRP level >40 mg/l in the first day under conditions of not using glucocorticoids manifests a risk of the development of infectious complications. Prolonged reduction of CRP from the 3rd day is characteristic of a favorable course of trauma disease, maintenance of the level or its elevation - of pyo-infectious complications. With the following development of sepsis CRP in blood during the first week is higher than 120 mg/l. The nonbacterial systemic inflammation response is determined on the 2nd day after trauma in 14.8% of casualties not being followed by the development of septic complications and in 44.5% - followed by sepsis. Glucocorticoids and specific immune medicines used in treatment of sepsis result in a reduced amount or complete disappearance of CRP in blood during administration of these medicines. Rejection of them is followed by the appearance of CRP in the amount showing the effect of treatment. Gradual reduction of CRP in sepsis associated with decreased activity of the infectious processes was observed only in casualties without a polyorganic insufficiency.

Adult↗

PubMed1989

Antenatal complications and perinatal outcome in patients with nausea and vomiting-complicated pregnancy.

The incidence of nausea and vomiting-complicated pregnancy was determined in a district hospital in Hong Kong. Nausea was present in 11.4% and vomiting in 63.5% of pregnant women. Patients with vomiting complicating early pregnancy have a statistically significant higher incidence of antepartum haemorrhage of indeterminate origin. The incidences of medical diseases complicating pregnancy, other major antenatal complications, and the neonatal outcome were not different between vomiting and non-vomiting patients.

Adult↗

PubMed1989

Complications of endodrainage retinotomies created during vitreous surgery for complicated retinal detachment.

The authors report nine cases of endodrainage retinotomy site complications that occurred after vitreous surgery for complicated retinal detachments (RDs). Postoperative subretinal neovascularization developed in four eyes at the retinotomy drainage site. In two eyes, postoperative proliferation at a posteriorly placed endodrainage site created traction macular detachments. Redetachment due to retinotomy opening caused by postoperative drainage site proliferation developed in three eyes. The retinas of all nine eyes were eventually reattached, and vision improved from the preoperative level. These complications are related to retinal pigment epithelium and/or Bruch's membrane damage during internal subretinal fluid drainage and retinotomy endolaser photocoagulation. Careful evaluation of extrusion instruments, drainage techniques, retinotomy placement, and subsequent endolaser treatment is necessary to minimize these complications.

Adolescent↗

PubMedDate not supplied

Assessment of long-term complications due to type 2 diabetes using patient self-report: the diabetes complications index.

This study aims to develop a patient-based measure of the complications of type 2 diabetes that can be used in examining its relationship with health-related quality of life (HRQOL) and utilization of health services. Using questions analogous to those typically employed by clinicians, we developed a 17-item questionnaire to identify prior diagnoses and current symptoms of 6 common complications of type 2 diabetes. We administered it to 419 patients with type 2 diabetes who were part of the Veterans Health Study, a larger prospective investigation of veterans receiving ambulatory care. From the responses, we calculated a simple sum of the 6 complications. We examined the correlation of this Diabetes Complications Index (DCI) with use of diabetes-related medical resources, outpatient doctor visits, HRQOL, duration of diabetes, and the degree to which patients perceived their health to be diminished by diabetes. The DCI was significantly correlated with the degree to which patients perceived their health to be diminished by diabetes (r = 0.35, P = .0001), utilization of diabetes-related resources (model R = 0.15, P = .0001), outpatient doctor visits (model R = .08, P = .001), and duration of diabetes (r = 0.11, P = .04). It had a good correlation with aspects of HRQOL that reflect physical function when controlling for age and comorbid conditions (model R = 0.23, P = .0001). The DCI shows promise as an efficient method for assessing the effects of type 2 diabetes on HRQOL and predicting utilization of medical resources.

Aged↗

PubMed2005

Hemoglobin A1c measurements over nearly two decades: sustaining comparable values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications study.

BACKGROUND: Clinical trials require assays that provide consistent results during the course of a study. The hemoglobin A1c (HbA1c) assay, a measure of chronic glycemia, is critical to the study of diabetes control and complications. METHODS: The Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), required 20 years of consistent HbA1c results, measured by three different ion-exchange HPLC procedures. To maintain and document consistent HbA1c results measured in the DCCT and EDIC Central Biochemistry Laboratory, a backup laboratory used frozen hemolysates as long-term calibrators and a HPLC method with a single lot of Bio-Rex 70 resin. RESULTS: Over 20 years, long-term quality-control values have remained constant. Four studies of nondiabetic ranges produced nearly identical values [mean (SD), 5.1 (0.5)%, 4.9 (0.3)%, 5.0 (0.4)%, and 5.0 (0.3)%]. CONCLUSION: The overall consistency of the HbA1c assays during the 20-year course of the DCCT and EDIC has been critical in establishing the benefits of intensive therapy and in understanding the relationship between long-term glycemia and the development and progression of the complications of diabetes.

Chromatography, High Pressure Liquid↗

PubMed2002

Genetic studies of late diabetic complications: the overlooked importance of diabetes duration before complication onset.

Genes play a role in many processes underlying late diabetic complications, but efforts to identify genetic variants have produced disappointing and contradictory results. Here, we evaluate whether the study designs and analytic methods commonly being used are optimal for finding susceptibility genes for diabetic complications. We do so by generating plausible genetic models and assessing the performance of case-control and family-based trio study designs. What emerges as a key determinant of success is duration of diabetes. This perspective focuses on duration of diabetes before complication onset and its influence on the ability to detect major and minor gene effects. It does not delve into the distinct effect of duration after complication onset, which can enrich case subjects with genotypes conferring survival advantage. We use clinically diagnosed nephropathy in type 1 diabetes to show how ignoring duration can result in considerable power loss in both case-control and family-based trio designs. We further show how, under certain circumstances, disregard for duration information can paradoxically lead to implicating nonrisk alleles as causative. Our results indicate that problems can be minimized by selecting case subjects with short diabetes duration and, to a lesser extent, control subjects with long duration or, perhaps, by adjusting for duration during analysis.

Case-Control Studies↗

PubMed2001

Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study.

OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

Adult↗

PubMed2002

Circulating and urinary transforming growth factor beta1, Amadori albumin, and complications of type 1 diabetes: the EURODIAB prospective complications study.

OBJECTIVE: Transforming growth factor (TGF)-beta1 is overexpressed in diabetes as a consequence of hyperglycemia and the creation of early glycated end products and may be responsible for the characteristic structural renal changes associated with diabetes. We sought to examine the role of both urinary and circulating TGF-beta1 and its promoter Amadori albumin in the vascular complications of type 1 diabetes. RESEARCH DESIGN AND METHODS: The present article reports on a nested case-control study from the EURODIAB Prospective Complications Study of Europeans with type 1 diabetes. Case subjects (n = 356) were all individuals with one or more complications of diabetes; control subjects (n = 185) were all individuals with no evidence of complications. RESULTS: Urinary TGF-beta1 and Amadori albumin were elevated in patients with micro- or macroalbuminuria. Standardized regression effects (SREs) for macroalbuminuria versus normoalbuminuria were 2.45 (95% CI 1.88-3.18, P = 0.0001 for urinary TGF-beta1) and 1.67 (1.34-2.07, P = 0.001 for Amadori albumin). The SRE for urinary TGF-beta1 remained statistically significant when adjusted for HbA(1c), Amadori albumin, and blood pressure. Circulating TGF-beta1 was elevated in individuals with proliferative retinopathy compared with individuals without retinopathy (SRE 1.29 [1.07-1.550], P = 0.007). This result was attenuated to 1.16 (0.95-1.43, P = 0.2) in the multivariate model, largely because of HbA(1c). CONCLUSIONS: Elevated levels of urinary TGF-beta1 in macroalbuminuria were associated with elevations in Amadori albumin and HbA(1c) and also in blood pressure. In contrast, only circulating TGF-beta1 was related to proliferative retinopathy, and HbA(1c) largely accounted for this. These findings may indicate novel pathways for understanding mechanisms and therapeutic interventions.

Adult↗