OBJECTIVE -Debate remains as to whether short-or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODS -A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C.RESULTS -Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63-3.14], P Ͻ 0.0001) and nephropathy (1.80 [1.37-2.42], P Ͻ 0.0001), with the relationship a feature in conventionally treated patients in particular.CONCLUSIONS -This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.

OBJECTIVE -The presence of insulin resistance and the metabolic syndrome are known risk markers for macrovascular disease in patients with and without type 2 diabetes. This study has examined whether these also were predictors of micro-and macrovascular complications in type 1 diabetic patients participating in the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS -International DiabetesFederation (IDF) criteria were used to identify the metabolic syndrome in 1,337 Caucasian DCCT patients at baseline. Insulin resistance was calculated using their estimated glucose disposal rate (eGDR). Insulin dose (units/kg) was also used as a separate marker of insulin resistance.RESULTS -The eGDR (but not insulin dose or metabolic syndrome) at baseline strongly predicted the development of retinopathy, nephropathy, and cardiovascular disease (hazard ratios 0.75, 0.88, and 0.70, respectively, per mg ⅐ kg Ϫ1 ⅐ min Ϫ1 change; P Ͻ 0.001, P ϭ 0.005, and P ϭ 0.002, respectively). Through mainly weight gain, the prevalence of the metabolic syndrome increased steadily from baseline to year 9 in conventionally treated (from 15.5 to 27.2%) and especially in the intensively treated (from 13.7 to 45.4%) patients.CONCLUSIONS -Higher insulin resistance at baseline in the DCCT (as estimated by eGDR) was associated with increased subsequent risk of both micro-and macrovascular complications. Insulin dose and the presence of IDF-defined metabolic syndrome were poor predictors by comparison. Although intensive treatment was associated with a higher subsequent prevalence of metabolic syndrome, the benefits of improved glycemia appear to outweigh the risks related to development of the metabolic syndrome. Diabetes Care 30:707-712, 2007T he metabolic syndrome is a cluster of metabolically related cardiovascular risk factors, the core components of which comprise of central obesity, insulin resistance, dyslipidemia, and hypertension (1). The presence of the metabolic syndrome predicts the risk of cardiovascular disease in nondiabetic subjects as well as in those with type 2 diabetes (2-6). There are multiple definitions for the metabolic syndrome (7-9), with the most recent being the consensus from the International Diabetes Federation (IDF) (10).Central to the development of the metabolic syndrome appears to be the presence of increased insulin resistance. Although this is a characteristic usually associated with the development of type 2 diabetes, it can also be a feature of patients with type 1 diabetes (11-13). When present in type 1 diabetes, the phrase "double diabetes" has been coined (14), with the assumption that these patients are likely to be at especially high risk of developing cardiovascular disease.Beyond the use of labor-intensive and invasive euglycemic-hyperinsulinemic clamp techniques, estimation of insulin resistance in type 1 diabetes is difficult because simpler tools such as the homeostasis model are not applicable for this group of patients (15). Clinically, insulin resistance in type 1 diabetic p...

OBJECTIVE -Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.RESULTS -Compliance with the dietary supplementation was Ͼ90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean Ϯ SD 8.09 Ϯ 21.9%, P ϭ 0.006), insulin resistance (6.47 Ϯ 27.7%, P ϭ 0.003), HbA 1c (0.64 Ϯ 3.19%, P ϭ 0.048), total cholesterol (4.07 Ϯ 8.13%, P ϭ 0.004), LDL cholesterol (7.09 Ϯ 12.7%, P ϭ 0.001), cholesterol/HDL cholesterol ratio (3.89 Ϯ 11.7%, P ϭ 0.015), and free thyroxine (2.50 Ϯ 8.47%, P ϭ 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.CONCLUSIONS -These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile. Diabetes Care 25:1709 -1714, 2002C ardiovascular diseases (CVDs), especially coronary heart disease and cerebrovascular disease, are the leading causes of death in women (1). Type 2 diabetes increases the risk of death from CVD by two-to fourfold (2), and women with diabetes are four times more likely to die from CVD than men (3). Postmenopausal estrogen depletion (4) and increased insulin resistance (5) may contribute to the high risk of accelerated CVD in women with type 2 diabetes.Epidemiological data suggest that in Japanese-Americans in Seattle, WA, the prevalence of type 2 diabetes is four times that in Japanese in Tokyo (6,7). Despite very similar degrees of hyperglycemia, the Japanese-Americans with type 2 diabetes showed significantly higher levels of plasma insulin after a 75-g oral glucose tolerance test (OGTT) than Japanese with diabetes (6,8), and BMI correlated with insulin levels only for the JapaneseAmerican men (8). This observation suggested a greater degree of insulin resistance among the Japanese-Americans and that factors other than BMI were responsible for the difference in plasma insulin levels between the two groups (9). Soy is a staple in the diet of the Japanese population, and consumption of soy has ...

OBJECTIVE -It is not known whether glycemic instability may confer a risk of microvascular complications that is in addition to that predicted by the mean blood glucose (MBG) value alone. This study has analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of glucose variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODS -Pre-and postprandial seven-point glucose profiles were collected quarterly during the DCCT in 1,441 individuals. The mean area under the curve glucose and the SD of glucose variability within 24 h and between visits were compared with the risk of retinopathy and nephropathy, having adjusted for age, sex, disease duration, treatment group, prevention cohort, and phase of treatment.RESULTS -Multivariate Cox regression showed that within-day and between-day variability in blood glucose around a patient's mean value has no influence on the development or progression of either retinopathy (P ϭ 0.18 and P ϭ 0.72, respectively) or nephropathy (P ϭ 0.32 and P ϭ 0.57). Neither preprandial (P ϭ 0.18) nor postprandial (P ϭ 0.31) glucose concentrations preferentially contribute to the probability of retinopathy.CONCLUSIONS -This study has shown that blood glucose variability does not appear to be an additional factor in the development of microvascular complications. Also, pre-and postprandial glucose values are equally predictive of the small-vessel complications of type 1 diabetes. Diabetes Care 29:1486 -1490, 2006I t is well established that the risk of developing the microvascular complications of diabetes is intimately related to the glycemic control of an individual. Having determined that HbA 1c (A1C) could be used as a surrogate marker for glycemia (1), both the Diabetes Control and Complications Trial (DCCT) in type 1 diabetes and the U.K. Prospective Diabetes Study in type 2 diabetes confirmed an exponential relationship between rising blood glucose and the risk of either developing or worsening retinopathy, nephropathy, and neuropathy (2-5). What is less clear is whether glycemic instability may confer a risk to complications that is in addition to that predicted by the mean glucose value alone. It is therefore unknown if two individuals with the same mean blood glucose (MBG), but extremes of glucose variability, might be expected to have the same or different complication risks.Circumstantial evidence from different studies gives conflicting conclusions as to whether variability in glucose values adds to the likelihood of complications. In favor of this association is the fact that in the DCCT, the rate of complications at a given value of A1C was higher in the conventionally treated patients than in those intensively treated (3). It was suggested that this may be a consequence of larger glycemic excursions in the former group of patients since they were on fewer injections of insulin per day. Also in support is another study where the incidence of retinopathy in a group of adolescents with type 1...

Aims/hypothesis The use of HbA 1c for the diagnosis of diabetes is now widely advocated despite caveats to its use.