Serum 8-hydroxy-guanine levels are increased in diabetic patients

OBJECTIVE: The production of reactive oxygen species is increased in diabetic patients, especially in those will poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker. RESEARCH DESIGN AND METHODS: We studied 41 type 2 diabetic patients and compared them with 3 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography. RESULTS: The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 +/- 0.69 vs. 0.96 +/- 0.15 pmol/ml P < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also could not and any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin exeretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria. CONCLUSIONS: Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes.     

Glycemic control is a predictor of survival for diabetic patients on hemodialysis

OBJECTIVE: To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS: This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 +/- 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c <7.5%, n = 93 (group G), and poor HbA1c > or = 7.5%, n = 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years. RESULTS: Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1. 133 per 1.0% increment of HbA1c, 95% CI 1.028-1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS: Good glycemic control (HbA1c <7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.     

Glycemic control in diabetes in three Danish counties.

BACKGROUND: Hemoglobin A1c (HbA1c) is a proxy measure for glycemic control in diabetes. We investigated the trend for glycemic control in patients from three Danish counties using HbA1c measurements. METHODS: We studied 2454 patients from a population of 807,000 inhabitants for whom routine monitoring of diabetes using HbA1c-DCCT aligned was initiated in 2001. We estimated the incidence of monitored patients in the population. The progress in patients with originally diabetic HbA1c levels was investigated by cumulative probability plots, and the individual trend in clinical outcome was investigated by a modified difference plot. RESULTS: The age-standardized incidence of monitored patients was <0.5% in all regions. Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. The overall percentage above the treatment target (>or=6.62% HbA1c) was 51% in 2003 compared to 59% in 2001, and the percentage with poor glycemic control (>or=10.0% HbA1c) was reduced from 19% to 4%. Of patients with originally diabetic HbA1c levels, 15% showed progress in glycemic control, and 28% reached treatment targets. In patients with originally normal HbA1c, 75% showed an upward trend in HbA1c levels, which reached diabetic concentrations in 17%. CONCLUSION: Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. In individual patients, 75% with originally diabetic HbA1c levels showed improved glycemic control after 3 years, while 78% with originally normal concentrations showed an upward trend in HbA1c levels.     

Correlation of periodontal inflamed surface area with glycemic status in controlled and uncontrolled type 2 diabetes mellitus

BACKGROUNDThe bidirectional link between periodontitis and diabetes mellitus (DM) has been established. Periodontitis causes systemic inflammatory burden through inflammatory mediators. The currently utilized tools [clinical attachment loss (CAL) and probing pocket depth (PPD)] are linear measurements, that do not exactly quantify the inflammatory burden of periodontitis. Periodontal inflamed surface area (PISA) quantifies the surface area of bleeding pocket epithelium and estimates the inflammatory burden. Studies relating to the periodontal status of diabetic patients with and without microvascular complications are scarce. This study assessed the proportion of periodontitis and correlation of PISA with glycemic status in controlled, uncontrolled type 2 DM (T2DM) with and without microvascular complications.AIMTo assess the proportion of periodontitis and correlation of PISA with glycemic status in controlled, and uncontrolled T2DM with and without microvascular complications.METHODSThis study comprised 180 T2DM patients. Based on glycated hemoglobin (HbA1c) levels, they were grouped into: (1) Controlled T2DMgroup: (HbA1c ≤ 7%); (2) Uncontrolled T2DM group: (HbA1c > 7%) without microvascular complications; and (3) Uncontrolled T2DM group: (HbA1c > 7%) with microvascular complications. Each group comprised 60 patients. All patients were assessed for periodontal parameters (Bleeding on Probing, PPD, CAL, Oral hygiene index simplified and PISA), and systemic parameters (HbA1c, fasting plasma glucose and post prandial plasma glucose).RESULTSThe proportion of periodontitis among controlled T2DM group, uncontrolled T2DM group without microvascular complications, uncontrolled T2DM group with microvascular complications was 75%, 93.4% and 96.6% respectively. Extent and severity of periodontitis were high in the uncontrolled T2DM group. A significant positive correlation was found between PISA and HbA1c among all patients (r = 0.393, P < 0.001). The dose–response relationship between PISA and HbA1c was observed. An increase of PISA with 168 mm² was associated with a 1.0% increase of HbA1c. CONCLUSIONHigh proportion and severity of periodontitis, and increased inflamed surface area in uncontrolled T2DM may have contributed to the poor glycemic control and microvascular complications.     

Racial differences in glycemic control in a well-functioning older diabetic population: findings from the Health,Aging and Body Composition Study

OBJECTIVE: To evaluate racial differences and factors associated with worse glycemic control in well-functioning older individuals with type 2 diabetes. Our hypothesis was that glycemic control would be worse among black than white diabetic individuals but that this association would be explained by differences in severity of diabetes, health status, health care indicators, and social, psychological, or behavioral factors. We further hypothesized that the association of race with poorer glycemic control would be limited to those with lower education or lower income. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of 468 diabetic participants among a cohort of 3,075 nondisabled blacks and whites aged 70-79 years living in the community enrolled in the Health, Aging and Body Composition Study. Glycemic control was measured by the level of HbA(1c). RESULTS: A total of 58.5% of the diabetic individuals were black. Although control was poor in all diabetic participants (HbA(1c) > or =7% in 73.7%), blacks had worse glycemic control than whites (age- and sex-adjusted mean HbA(1c), 8.4% in blacks and 7.4% in whites; P < 0.01). Race differences in glycemic control remained significant, even after adjusting for current insulin therapy, cardiovascular disease, higher total cholesterol, and not receiving a flu shot in the previous year, all of which were associated with higher HbA(1c) concentrations. Controlling for these factors reduced the association by 27%. Race remained an important factor in glycemic control, even when results were stratified by education or income. CONCLUSIONS: HbA(1c) concentrations were higher in older black diabetic individuals. Differences in glycemic control by race were associated with disease severity, health status, and poorer quality of care, but these factors did not fully explain the higher HbA(1c) levels in older black diabetic individuals.     

Clinical and psychological course of diabetes from adolescence to young adulthood: a longitudinal cohort study

OBJECTIVE: To determine the clinical and psychological course of diabetes through adolescence and the relationship with glycemic control in young adulthood. RESEARCH DESIGN AND METHODS: A longitudinal cohort study of adolescents recruited from the register of the outpatient pediatric diabetes clinic. A total of 76 individuals (43 male patients, 33 female patients) aged 11-18 years completed baseline assessments, and 65 individuals (86%) were reinterviewed as young adults (20-28 years of age). Longitudinal assessments were made of glycemic control (HbA(1c)), weight gain (BMI), and development of complications. Adolescents completed self-report questionnaires to assess emotional and behavioral problems as well as self-esteem. As young adults, psychological state was assessed by the Revised Clinical Interview Schedule and the self-report Brief Symptom Inventory. RESULTS: Mean HbA(1c) levels peaked in late adolescence and were worse in female participants (average 11.1% at 18-19 years of age). The proportion of individuals who were overweight (BMI >25.0 kg/m(2)) increased during the 8-year period from 21 to 54% in female patients and from 2 to 28% in male patients. Serious diabetes-related events included death in one patient and cognitive impairment in two patients. Individuals in whom diabetic complications developed (25% of male patients and 38% of female patients) had significantly higher mean HbA(1c) levels than those without complications (difference 1.9%, 95% CI 1.1-2.7, P < 0.0001). Behavioral problems at baseline were related to higher mean HbA(1c) during the subsequent 8 years (beta = 0.15, SEM (beta) 0.04, P < 0.001, 95% CI 0.07-0.24). CONCLUSIONS: The outcome for this cohort was generally poor. Behavioral problems in adolescence seem to be important in influencing later glycemic control.     

Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden

OBJECTIVE: The aim of this work was to study the impact of glycemic control (HbA(1c)) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: All children, diagnosed at 0-14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA(1c) and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports. RESULTS: During the follow-up period, with a mean duration of 12 +/- 4 years (range 5-19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA(1c)) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA(1c) during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5-11 and >11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power. CONCLUSIONS: Despite modern insulin treatment, >50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after approximately 12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.     

Effect of puberty on insulinlike growth factor I and HbA1 in type I diabetes.

OBJECTIVE: To assess the effect of puberty on the relationship between glycemic control and insulinlike growth factor I (IGF-I) levels in children with insulin-dependent (type I) diabetes mellitus. RESEARCH DESIGN AND METHODS: Simultaneous HbA1 and plasma IGF-I levels were determined in 71 prepubertal (Tanner stage I) and 112 pubertal (Tanner stages II-V) subjects aged 2.7-17.8 yr. RESULTS: Overall, IGF-I levels were positively correlated with both age (r = 0.31, P less than 0.001) and Tanner stage (r = 0.32, P less than 0.001) but only weakly associated with HbA1 values (r = -0.16, P = 0.025). A strong negative association existed between IGF-I and HbA1 levels (r = -0.45, P less than 0.001) in the pubertal subjects, but no such association was apparent in the prepubertal subjects. Multiple regression analyses disclosed a significant independent negative association between IGF-I and HbA1 levels in the pubertal group (P less than 0.001) but not in the prepubertal group. CONCLUSIONS: Glycemic control appears to strongly influence IGF-I levels only after the onset of puberty.     

Improvement in glycemic control over 11 years in patients monitored for diabetes in one county.

BACKGROUND: Hemoglobin A(1c) (HbA(1c)) has been used in controlled trials for the last 10 years but has never been evaluated in clinical practice as an effective parameter for clinical outcome. We investigated the trend for glycemic control over 11 years in one county of 350,000 citizens. METHODS: We studied 226,382 HbA(1c-DCCT-aligned) from 39,455 patients in whom routine monitoring for diabetes was initiated in 1993, 1996, or 2001. The trend in glycemic control was investigated in groups by probit plots, and in individual patients by target plots. RESULTS: From 1993 to 2001, the number of HbA(1c) measurements increased three-fold. The number of new monitoring series increased from 0.22% to 0.27% of the county population, and the number of patients monitored using HbA(1c) as a proxy for diabetes increased from 0.5% to 1.5%. A proportional reduction in high HbA(1c) concentrations of 5% was identified in the 1993 group, compared to 15% in the 1996 group, and 20% in the 2001 group. The percentage of patients with diabetic first HbA(1c) experiencing normalization increased from 8% to 30% for males and from 9% to 24% for females (1993-2001). The percentage of HbA(1c) concentrations that were not normalized decreased from 78% to 53% for males and from 83% to 59% for females (1993-2001). The median HbA(1c) at initiation of monitoring decreased from 8.7% in 1993 to 7.5% in 2001 (p < 10(-5)). The number of normal first HbA(1c) results in monitoring series increased from 7% to 17% for males and from 8% to 22% for females. Up to 10% of subjects developed diabetic concentrations during monitoring. CONCLUSION: On average, patients with diabetic first HbA(1c) concentrations (> or =6.62%) showed an improvement in glycemic control from 5% in 1993 to 20% in 2001. High concentrations were easiest to reduce. In patients with originally diabetic HbA(1c) levels, 66% on average showed improved glycemic control in the 2001 series compared to 50% in the 1993 series. An average of 6% (1993) vs. 9% (2001) with originally normal HbA(1c) levels showed an upward trend inHbA(1c) levels. Median HbA(1c) at initiation of monitoring decreased from 8.7% in 1993 to 7.5% in 2001 (p < 10(-5)). The incidence of new cases was constant.     

Antidiabetic prescriptions and glycemic control in German patients with type 2 diabetes mellitus: a retrospective database study

OBJECTIVES: This study examined patterns of antidiabetic treatment among individuals with type 2 diabetes in Germany and investigated potential differences in attainment of glycemic control associated with the use of specific antidiabetic regimens. METHODS: This was a retrospective database study. Data were obtained from the German IMS Disease Analyzer-MediPlus database. Patients aged >or=20 years who were identified as having type 2 diabetes and who underwent glycosylated hemoglobin (HbA(1c)) testing at least once between April 1, 2004, and December 31, 2004, were included in the analyses. Potential associations between age, sex, and diabetic complications and the use of specific antidiabetic medications were examined. Also examined were potential associations between attainment of the HbA(1c) target for glycemic control (56.5%), particular patient characteristics, and the use of specific antidiabetic medications. RESULTS: The study included data from 5135 patients with type 2 diabetes (mean age, 67 years; 2702 men, 2433 women; mean [SD] HbA(1c), 6.9% [1.2%]). The most commonly diagnosed comorbidities were hypertension (66.5%) and obesity (18.7%). There were no significant differences in mean age, sex, or comorbidities between patients categorized by HbA(1c) values 6.5%. The most commonly prescribed antidiabetic medications were metformin (20.4%), a sulfonylurea (11.7%), and oral combination therapy (10.9%). In the assessment of potential associations between selected patient characteristics and the receipt of specific antidiabetic medications, individuals were less likely to receive metformin monotherapy if they were aged >or=75 years (12.0%, compared with 21.4% of those aged 65-74 years and 24.7% of those aged <65 years; P < 0.001) or had a diagnosis of a diabetic complication (15.9%, compared with 21.2% in those without complications; P < 0.001). Among those who were more likely to receive insulin monotherapy were women (11.5%, compared with 9.6% of men; P = 0.025) and patients with diabetic complications (13.9%, compared with 9.8% of those without complications; P < 0.001). More than half (52.7%) of patients did not attain the HbA(1c) target. There were significant differences between patients attaining the HbA(1c) target and receipt of specific antidiabetic medications (P < 0.001). Patients treated with insulin monotherapy or oral plus insulin combination therapy were least likely to reach the HbA(1c) target (26.4% and 22.9%, respectively, attained glycemic control; both, P < 0.001). Only 179 (31.9%) of 562 patients treated with oral combination therapy achieved the HbA(1c) target (P < 0.001). CONCLUSIONS: Over half of these German patients with type 2 diabetes failed to attain the HbA(1c) target for glycemic control. Patients who were prescribed insulin monotherapy or combination therapy were least likely to achieve the target.     

Leptin levels and body composition in children and adolescents with type 1 diabetes

The purpose of this study was to determine the relationship between serum leptin levels and body composition and to evaluate the variables related to disease in children and adolescents with type 1 diabetes. We studied 49 diabetic patients aged 6-16 years (age: 11.2+/-2.9 years, M/F: 26/23), and 37 healthy controls. Body composition was determined by dual-energy X-ray absorptiometry. Serum leptin, glycated hemoglobin (HbA1c), free thyroxin, thyrotropin, testosterone and estradiol levels were measured in patients and controls. We did not observe significant difference in serum leptin levels between patients and controls. Girls had significantly higher serum leptin levels than boys in both patient and control groups. Serum leptin levels did not correlate significantly with HbA1c, disease duration or daily insulin dose but, correlated positively with body mass index (BMI) and fat mass (FM) in patients as in controls. Body composition in diabetic girls and boys was similar with respective controls. When analyzed by pubertal stage, BMI, lean body mass (LBM), FM, and total bone mineral density (BMD) were significantly higher in pubertal girls with type 1 diabetes compared to prepubertal ones. In pubertal boys with type 1 diabetes, LBM and FM were significantly higher than prepubertal ones. The results of the present study showed that neither serum leptin levels nor body composition was significantly altered in children and adolescents with type 1 diabetes managed with intensive insulin therapy.     

Association among individual deprivation, glycemic control, and diabetes complications: the EPICES score

OBJECTIVE: Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 +/- 13.2 years [mean +/- SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed. RESULTS: HbA(1c) level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (beta = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05-5.43], P = 0.037), retinopathy (3.66 [1.39-9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14-0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors. CONCLUSIONS: Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high.     

Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men

OBJECTIVE: Erectile dysfunction is frequently observed in diabetes. The current study aims to assess the association of a comprehensive set of clinical, socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic men. RESEARCH DESIGN AND METHODS: Participants were randomly selected from male patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants completed a self-reported questionnaire on demographic, socioeconomic, and lifestyle characteristics and on erectile function, using the IIEF-15 (International Index of Erectile Function). Information on diabetes type, duration, treatment, and control; microvascular complications and cardiovascular disease; drug therapy; blood pressure; and lipid levels was also obtained. RESULTS: Information on erectile function was obtained in 1,040 patients. Their mean age was 57 years, and their median diabetes duration was 8 years (range <1-50). Normal erectile function was found in 13.5% of the patients and severe erectile dysfunction in 30.1%. The characteristics found to be significantly associated with erectile dysfunction [associations presented as adjusted odds ratio (95% CI)] were: patient's age (5-year increments): 1.38 (1.29-1.48); diabetes duration (5-year increments): 1.16 (1.07-1.26); current HbA(1c) level (1% increment): 1.10 (1.01-1.19); any microvascular disease: 1.43 (1.09-1.88); cardiovascular disease: 1.78 (1.27-2.48); and diuretic treatment: 1.78 (1.09-2.91). Leisure time and work-related physical activity and consumption of small amounts of alcohol were found to be protective: 0.51 (0.36-0.72) and 0.70 (0.51-0.97), respectively. CONCLUSIONS: In diabetic men, erectile dysfunction severity increases with age and diabetes duration, poor glycemic control, presence of microvascular complications, diuretic treatment, and cardiovascular disease. Physical activity and alcohol intake may be protective. These findings can guide clinicians in taking preventive measures and undertaking early screening and treatment in high-risk patients.     

Blood letting in high-ferritin type 2 diabetes: effects on vascular reactivity

OBJECTIVE: In a recent study, iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease. We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration. RESEARCH DESIGN AND METHODS: A total of 28 type 2 diabetic male patients with serum ferritin levels >200 ng/ml ( approximately 18% of consecutive type 2 diabetic men attending our outpatient clinic) were randomized to iron depletion (three extractions of 500 ml blood at 2-week intervals; group 1A) or to observation (group 1B). C282Y mutation was absent in all patients. Vascular reactivity (high-resolution external ultrasound) was evaluated at baseline and at 4 and 12 months thereafter. The two groups of patients were matched for age, BMI, pharmacological treatment, and chronic diabetic complications. RESULTS: Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients. In contrast, the vasodilation induced by glyceryl trinitrate (GTN) improved significantly after iron depletion (P = 0.006). These changes occurred in parallel to decreases in transferrin saturation index and HbA(1c) levels (-0.6%, P < 0.05) only in group 1A patients. The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA(1c) levels. Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin (r = -0.45, P = 0.04). At 12 months, transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects. CONCLUSIONS: Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations. The mechanisms by which these changes occur should be further investigated.     

Effect of oxidized lipids in the diet on oxidized lipid levels in postprandial serum chylomicrons of diabetic patients.

OBJECTIVE: To determine whether humans with type 2 diabetes have increased levels of oxidized fatty acids in their serum chylomicron fraction after the ingestion of dietary oxidized fatty acids. RESEARCH DESIGN AND METHODS: The study was performed on 31 male type 2 diabetic patients and 24 age-matched control subjects. Among the diabetic patients, 22 had poor glycemic control, defined as HbA1 > 10% (normal value < 7.7%). Nine patients had good glycemic control (HbA1 < or = 10). Heated corn oil containing low or high levels of oxidized fatty acids was used as a test meal. At 2.5 h after the test meal, 50-ml blood samples were obtained from all subjects, and the chylomicron fraction (Sf > 1,000) was isolated. The degree of oxidation in chylomicrons was determined by measuring conjugated dienes. For determining the postprandial levels of triglycerides and of oxidized lipids in serum chylomicrons over an extended time period, blood samples were obtained at 0, 2.5, 5.0, and 7.5 h for isolation of chylomicrons and determination of fatty acid oxidation. RESULTS: We found that at 2.5 h after the consumption of the test meal containing either a low or high oxidized fatty acid content, conjugated dienes in serum chylomicrons in diabetic subjects in poor glycemic control were increased compared with those in control subjects. Diabetic patients in good glycemic control had similar levels of oxidized lipid in their chylomicrons when compared with control subjects. Additionally, in diabetic patients in poor glycemic control, the levels of oxidized lipids in chylomicrons remained elevated for an extended post-prandial period. CONCLUSIONS: In diabetic subjects with poor glycemic control, dietary oxidized lipids induce an exaggerated and sustained increase in the levels of oxidized lipids in chylomicrons when compared with either control subjects or diabetic patients with good glycemic control. These increased postprandial levels of potentially atherogenic oxidized lipids may contribute to the accelerated atherosclerosis associated with diabetes.     

初诊2型糖尿病患者HbA1c与血清MCP-1、MMP-9的相关性研 究简

目的：探讨初诊2型糖尿病患者糖化血红蛋白A1c（HbA1c）与血清单核细胞趋化蛋白-1（MCP-1）、基质金属蛋白-9（MMP-9）的相关性及其临床价值。方法同期对103例初诊2型糖尿病患者（糖尿病组）和103例健康志愿者（对照组）的HbA1c水平及血清MCP-1和MMP-9进行检测和相关性分析。结果糖尿病组患者的HbA1c及血清MCP-1和MMP-9水平,均明显高于对照组,差异均有统计学意义（t分别=17.04、7.23、10.28,P均＜0.05）。糖尿病患者血清MCP-1和MMP-9均与HbA1c呈正相关性（r分别=0.75、0.74、P均＜0.05）。结论即使对于初诊2型糖尿病患者,也应全面筛查和评估有无发生糖尿病并发症和相关风险性;监测HbA1c也可间接反映患者体内免疫炎症反应的强度及并发症发生情况。     

Increased urinary transferrin excretion predicts microalbuminuria in patients with type 2 diabetes.

OBJECTIVE: We studied whether increased urinary transferrin excretion rates (TERs) (urinary transferrin-to-urinary creatinine ratio > or = 107 micrograms/mmol, which is the sum of an average and 2 SDs in 431 healthy nondiabetic individuals) would predict the development of microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2.8 mg/mmol) in patients with type 2 diabetes and normal urinary albumin excretion rates (AERs) (albumin-to-creatinine ratio < 2.8 mg/mmol). We also studied the influence of blood pressure, glycemic control, and serum levels of lipids and apolipoproteins on the later development of microalbuminuria. RESEARCH DESIGN AND METHODS: In 77 diabetic patients with normal AER, AER and TER were measured at baseline and after 24 months of follow-up. Blood pressure, glycemic control, and serum levels of lipids and apolipoproteins were measured at 1- to 2-month intervals during the follow-up period. RESULTS: Of the 16 patients who initially had increased TER, 5 (31%) developed microalbuminuria. In contrast, of the 61 who initially had normal TER, 4 (7%) developed microalbuminuria (P = 0.016). At baseline, no difference was found in age, sex, diabetes duration, diabetic medications, prevalence of hypertension, blood pressure, HbA1c levels, or serum lipid and apolipoprotein concentrations between the two group of patients with normal and increased TER. There was also no difference in duration of hypertension and prevalence of users of ACE inhibitors between two subgroups of hypertensive patients with normal and increased TER. During the 24 month follow-up period, those whose condition progressed to microalbuminuria had increased serum levels of triglycerides (1.87 +/- 0.49 vs. 1.29 +/- 0.64 mmol/l, P = 0.003) and apolipoprotein B (114 +/- 20 vs. 102 +/- 24 mg/dl, P = 0.05) and tended to have increased HbA1c levels (7.7 +/- 1.0 vs. 7.1 +/- 1.1%, P = 0.10) compared with those in whom microalbuminuria did not develop. Blood pressure, however, did not differ. In multivariate stepwise logistic regression analysis, the association between increased TER at baseline and subsequent development of microalbuminuria was significant (odds ratio 7.04 [95% CI 1.02-48.5], P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and normal AER, increased TER may predict the development of microalbuminuria and abnormalities in triglyceride-rich lipoprotein metabolism, and poor glycemic control may be associated with this progression.     

Glycemic control and bone age are independently associated with muscle capillary basement membrane width in diabetic children after puberty

This study was undertaken to examine the possible relationships between muscle capillary basement membrane width (CBMW) and glycemic control, bone age, chronologic age, and duration of diabetes in young patients with insulin-dependent diabetes mellitus (IDDM) during different stages of pubertal development. We studied 49 males and 43 females (age, 7-20 yr) with IDDM for up to 16 yr for whom bone age and glycosylated hemoglobin (HbA1c) data were available at the time of right quadriceps muscle biopsy. Based on pubic hair Tanner stage, subjects were assigned to prepubertal (Tanner I), pubertal (Tanner II and III), and postpubertal (Tanner IV and V) groups. In 30 pubertal and prepubertal subjects, none of the variables studied was significantly correlated with CBMW. This is attributable in part to the small number of subjects in each group. In 62 postpubertal subjects, CBMW was correlated with age (r = .27, P = .03), bone age (r = .43, P = .0005), and postpubertal duration of diabetes (r = .38, P = .003) but not total duration of diabetes. In the postpubertal subjects, CBMW was correlated with HbA1c at the time of biopsy (r = .31, P = .01) but correlated more strongly with the mean of HbA1c values obtained during the 1- and 2-yr periods before biopsy (r = .37, P = .01, and r = .54, P = .03, respectively). An analysis of covariance revealed that the slopes for the regression of loge CBMW on HbA1c differed significantly (P = .02) among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum 1,5-anhydro-D-glucitol and glycemic control in patients with non-insulin-dependent diabetes mellitus

Serum 1,5-anhydro-D-glucitol (AG) levels, which have been reported to decrease specifically in diabetics, were measured in 102 patients with non-insulin-dependent diabetes mellitus (NIDDM). The mean of serum AG levels was 7.9 +/- 0.7 micrograms/ml (mean +/- S.E.). It was found a significant negative correlation between serum AG level and HbA1c or fasting blood sugar level. The decrease in serum AG levels inversely correlated with the extent of glycemic control in the patients with NIDDM. Additionally, the changes of serum AG levels negatively correlated with the changes of HbA1c levels during long-term (2 years) treatment. Furthermore, serum AG levels were compared between the patients with and without diabetic complication such as retinopathy, proteinuria or neuropathy. It was found that each group of the patients with complication had significantly decreased serum AG level compared with the complication free group. On the other hand, however, no differences were found in serum AG levels corrected by HbA1c levels using the linear regression formula between the group of the patients with and without diabetic complication.     

Developing a prediction rule from automated clinical databases to identify high-risk patients in a large population with diabetes

OBJECTIVE: To develop and validate a prediction rule for identifying diabetic patients at high short-term risk of complications using automated data in a large managed care organization. RESEARCH DESIGN AND METHODS: Retrospective cohort analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern California, aged > or =19 years. Data from 1994 to 1995 were used to model risk for macro- and microvascular complications (n = 3,977), infectious complications (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory records, pharmacy records, utilization records, and survey data. Using split-sample validation, the risk scores derived from logistic regression models in half of the population were evaluated in the second half. Sensitivity, positive predictive value, and receiver operating characteristics curves were used to compare scores obtained from full models to those derived using simpler approaches. RESULTS: History of prior complications or related outpatient diagnoses were the strongest predictors in each complications set. For patients without previous events, treatment with insulin alone, serum creatinine > or =1.3 mg/dl, use of two or more antihypertensive medications, HbA(1c) >10%, and albuminuria/microalbuminuria were independent predictors of two or all three complications. Several risk scores derived from multivariate models were more efficient than simply targeting patients with elevated HbA(1c) levels for identifying high-risk patients. CONCLUSIONS: Simple prediction rules based on automated clinical data are useful in planning care management for populations with diabetes.