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OBJECTIVE Type 2 diabetes is an established risk factor for dementia. However, the roles of glycemic control and diabetic complications in the development of dementia have been less well substantiated. This large-scale cohort study aims to examine associations of longitudinal HbA1c levels and diabetic complications with the risk of dementia incidence among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Data of eligible patients with diabetes, aged ≥50 years in the U.K. Clinical Practice Research Datalink from 1987 to 2018, were analyzed. Time-varying Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% CIs for dementia risk. RESULTS Among 457,902 patients with diabetes, 28,627 (6.3%) incident dementia cases were observed during a median of 6 years’ follow-up. Patients with recorded hypoglycemic events or microvascular complications were at higher risk of dementia incidence compared with those without such complications (HR 1.30 [95% CI 1.22–1.39] and 1.10 [1.06–1.14], respectively). The HbA1c level, modeled as a time-varying exposure, was associated with increased dementia risk (HR 1.08 [95% CI 1.07–1.09] per 1% HbA1c increment) among 372,287 patients with diabetes with postdiagnosis HbA1c records. Similarly, a higher coefficient of variation of HbA1c during the initial 3 years of follow-up was associated with higher subsequent dementia risk (HR 1.03 [95% CI 1.01–1.04] per 1-SD increment). CONCLUSIONS Higher or unstable HbA1c levels and the presence of diabetic complications in patients with type 2 diabetes are associated with increased dementia risk. Effective management of glycemia might have a significant role in maintaining cognitive health among older adults with diabetes.

OBJECTIVE Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed. RESEARCH DESIGN AND METHODS In the Maastricht Study, a type 2 diabetes–enriched population-based cohort study (1,361 subjects with normal glucose metabolism, 348 with prediabetes, and 510 with type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors. RESULTS Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = −0.055 [95% CI −0.172, 0.062], stβType2diabetes = −0.256 [−0.379, −0.133], Ptrend < 0.001). Prediabetes was associated with lower local efficiency (stβ = −0.084 [95% CI −0.159, −0.008], P = 0.033) and lower clustering coefficient (stβ = −0.097 [95% CI −0.189, −0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008). CONCLUSIONS These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections.

OBJECTIVE Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. RESEARCH DESIGN AND METHODS Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0–2, 3–4, and 5–6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. RESULTS There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0–25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. CONCLUSIONS Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.

OBJECTIVE: Diagnosing bone infection in the diabetic foot is challenging and often requires several diagnostic procedures, including advanced imaging. We compared the diagnostic performances of MRI, radiolabeled white blood cell (WBC) scintigraphy (either with (99m)Tc-hexamethylpropyleneamineoxime [HMPAO] or (111)In-oxine), and [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)/computed tomography.RESEARCH DESIGN AND METHODS: We searched Medline and Embase as of August 2016 for studies of diagnostic tests on patients known or suspected to have diabetes and a foot infection. We performed a systematic review using criteria recommended by the Cochrane Review of a database that included prospective and retrospective diagnostic studies performed on patients with diabetes in whom there was a clinical suspicion of osteomyelitis of the foot. The preferred reference standard was bone biopsy and subsequent pathological (or microbiological) examination.RESULTS: Our review found 6,649 articles; 3,894 in Medline and 2,755 in Embase. A total of 27 full articles and 2 posters was selected for inclusion in the analysis. The performance characteristics for the (18)F-FDG-PET were: sensitivity, 89%; specificity, 92%; diagnostic odds ratio (DOR), 95; positive likelihood ratio (LR), 11; and negative LR, 0.11. For WBC scan with (111)In-oxine, the values were: sensitivity, 92%; specificity, 75%; DOR, 34; positive LR, 3.6; and negative LR, 0.1. For WBC scan with (99m)Tc-HMPAO, the values were: sensitivity, 91%; specificity, 92%; DOR, 118; positive LR, 12; and negative LR, 0.1. Finally, for MRI, the values were: sensitivity, 93%; specificity, 75%; DOR, 37; positive LR, 3.66, and negative LR, 0.10.CONCLUSIONS: The various modalities have similar sensitivity, but (18)F-FDG-PET and (99m)Tc-HMPAO-labeled WBC scintigraphy offer the highest specificity. Larger prospective studies with a direct comparison among the different imaging techniques are required.

OBJECTIVE People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2–12.0) before and 19.4/1,000 person-years (95% CI 11.9–23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1–42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6–35.0%) in those who progressed to type 2 diabetes in 10–20 years, and 13.9% (95% CI 7.0–20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18–2.52]). CONCLUSIONS As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

OBJECTIVE Poor glycemic control is related to vascular events in patients with type 2 diabetes, but the presence of vascular disease might influence this relation. We evaluated the relation between glycemic control (HbA1c level) and new cardiovascular events and mortality in patients with type 2 diabetes, with and without vascular disease. RESEARCH DESIGN AND METHODS In a cohort of 1,687 patients with type 2 diabetes enrolled in the Second Manifestations of Arterial Disease (SMART) study, the continuous relation between HbA1c and cardiovascular events (composite of myocardial infarction, stroke, and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses stratified for the presence of vascular disease. RESULTS During a median follow-up time of 6.1 years (interquartile range 3.1–9.5 years), a new cardiovascular event developed in 293 patients and 340 patients died. In all patients, the hazard ratio (HR) of the relation between HbA1c level and cardiovascular events was 1.06 (95% CI 0.97–1.17). A 1 percentage point higher HbA1c level was related to a 27% higher risk of a cardiovascular event in patients with type 2 diabetes without vascular disease (HR 1.27 [95% CI 1.06–1.51]), but not in patients with vascular disease (HR 1.03 [95% CI 0.93–1.15], P for interaction = 0.195). A 1 percentage point higher HbA1c level was related to a 16% higher risk of death (HR 1.16 [95% CI 1.06–1.28]) in patients with vascular disease and a nonsignificant 13% higher risk of all-cause mortality (HR 1.13 [95% CI 0.97–1.31]) in patients without vascular disease. CONCLUSIONS In patients with type 2 diabetes, there is a modest, but not statistically significant, relation between HbA1c level and cardiovascular events, and, as there was no statistically significant interaction, this relation was not different for patients with or without clinical manifestation of vascular disease.

OBJECTIVE There are limited data about the effects of sodium–glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies. The primary end point of this substudy was the change in HbA1c from baseline at 18 weeks among patients using insulin; 52-week effects were also examined. RESULTS Individuals receiving insulin at baseline were randomized to receive placebo (n = 690), canagliflozin 100 mg (n = 692), or canagliflozin 300 mg (n = 690). These individuals were 66% male and had a median age of 63 years, mean HbA1c of 8.3% (67 mmol/mol), BMI of 33.1 kg/m2, estimated glomerular filtration rate of 75 mL/min/1.73 m2, fasting plasma glucose of 9.2 mmol/L, and a median daily insulin dose of 60 IU. Most individuals were using basal/bolus insulin. Reductions in HbA1c with canagliflozin 100 and 300 mg versus placebo were −0.62% (95% CI −0.69, −0.54; −6.8 mmol/mol [95% CI −7.5, −5.9]; P < 0.001) and −0.73% (95% CI −0.81, −0.65; −8.0 mmol/mol [95% CI −8.9, −7.1]; P < 0.001) at 18 weeks and −0.58% (95% CI −0.68, −0.48; −6.3 mmol/mol [95% CI −7.4, −5.2]) and −0.73% (95% CI −0.83, −0.63; −8.0 mmol/mol [95% CI −9.1, −6.9]) at 52 weeks. There were significant falls in fasting plasma glucose, body weight, and blood pressure at both time points and there was a greater incidence of hypoglycemia, genital mycotic infections, and hypovolemia with both canagliflozin doses. CONCLUSIONS Canagliflozin added to insulin therapy improved glycemic control and decreased body weight. There was a greater frequency of several anticipated side effects, although few led to discontinuation of treatment.

OBJECTIVE To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial. RESEARCH DESIGN AND METHODS A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years. RESULTS ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385–7,175); however, these were not evident among individuals with a history of cardiovascular disease. CONCLUSIONS Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.

OBJECTIVE To assess whether after the introduction of diabetes performance measures decreases in undertreatment correspond with increases in overtreatment for blood pressure (BP) and glycemic control in different patient age groups. RESEARCH DESIGN AND METHODS We conducted a cohort study using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. General practices were included when data were available from 1 year before to at least 1 year after the introduction of diabetes performance measures. Included patients had a confirmed diagnosis of type 2 diabetes. Potential overtreatment was defined as prescribing maximum treatment or a treatment intensification to patients with a sustained low-risk factor level. Potential undertreatment was defined as a lack of treatment intensification in patients with a sustained high-risk factor level. Percentages of over- and undertreated patients at baseline were compared with those in subsequent years, and stratified analyses were performed for different patient age groups. RESULTS For BP, undertreatment significantly decreased from 61 to 57% in the first year after the introduction of performance measures. In patients >75 years of age, undertreatment decreased from 65 to ∼61%. Overtreatment was relatively stable (∼16%). For glycemic control, undertreatment significantly increased from 49 to 53%, and overtreatment remained relatively stable (∼7%). CONCLUSIONS The improvement of BP undertreatment after introduction of the performance measures did not correspond with an increase in overtreatment. The performance measures appeared to have little impact on improving glucose-regulating treatment. The trends did not differ among patient age groups.

OBJECTIVE Depression is a common comorbidity of diabetes, undesirably affecting patients’ physical and mental functioning. Psychological interventions are effective treatments for depression in the general population as well as in patients with a chronic disease. The aim of this study was to assess the efficacy of individual mindfulness-based cognitive therapy (MBCT) and individual cognitive behavior therapy (CBT) in comparison with a waiting-list control condition for treating depressive symptoms in adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled trial, 94 outpatients with diabetes and comorbid depressive symptoms (i.e., Beck Depression Inventory-II [BDI-II] ≥14) were randomized to MBCT (n = 31), CBT (n = 32), or waiting list (n = 31). All participants completed written questionnaires and interviews at pre- and postmeasurement (3 months later). Primary outcome measure was severity of depressive symptoms (BDI-II and Toronto Hamilton Depression Rating Scale). Anxiety (Generalized Anxiety Disorder 7), well-being (Well-Being Index), diabetes-related distress (Problem Areas In Diabetes), and HbA1c levels were assessed as secondary outcomes. RESULTS Results showed that participants receiving MBCT and CBT reported significantly greater reductions in depressive symptoms compared with patients in the waiting-list control condition (respectively, P = 0.004 and P < 0.001; d = 0.80 and 1.00; clinically relevant improvement 26% and 29% vs. 4%). Both interventions also had significant positive effects on anxiety, well-being, and diabetes-related distress. No significant effect was found on HbA1c values. CONCLUSIONS Both individual MBCT and CBT are effective in improving a range of psychological symptoms in individuals with type 1 and type 2 diabetes.

OBJECTIVE Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality. RESULTS We included 1,195 patients (age 67 ± 12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1–9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2–10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99–1.39]; P = 0.068) and all-cause mortality (1.22 [1.09–1.36]; P = 0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR −0.27 to 0.55%]) and all-cause mortality (0.77% [0.17–1.37%]) beyond currently used clinical markers. CONCLUSIONS We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake.

OBJECTIVE Chronic exposure to calcineurin inhibitors and corticosteroids poses renal transplant recipients (RTR) at high risk for development of new-onset diabetes after transplantation (NODAT). Pancreatic β-cell dysfunction may be crucial to the pathophysiology of NODAT and specific markers for β-cell dysfunction may have additive value for predicting NODAT in this population. Therefore, we prospectively investigated whether proinsulin, as a marker of pancreatic β-cell dysfunction, is associated with future development of NODAT and improves prediction of it. RESEARCH DESIGN AND METHODS All RTR between 2001 and 2003 with a functioning graft for ≥1 year were considered eligible for inclusion, except for subjects with diabetes at baseline who were excluded. We recorded incidence of NODAT until April 2012. RESULTS A total of 487 RTR (age 50 ± 12 years, 55% men) participated at a median time of 6.0 (interquartile range [IQR], 2.6–11.5) years after transplantation. Median fasting proinsulin levels were 16.6 (IQR, 11.0–24.2) pmol/L. During median follow-up for 10.1 (IQR, 9.1–10.4) years, 42 (35%) RTR had development of NODAT in the highest quartile of the distribution of proinsulin versus 34 (9%) in the lowest three quartiles (P < 0.001). In Cox regression analyses, proinsulin (hazard ratio, 2.29; 95% CI, 1.85–2.83; P < 0.001) was strongly associated with NODAT development. This was independent of age, sex, calcineurine inhibitors, prednisolone use, components of the metabolic syndrome, or homeostasis model assessment. CONCLUSIONS In conclusion, fasting proinsulin is strongly associated with NODAT development in RTR. Our results highlight the role of β-cell dysfunction in the pathophysiology of NODAT and indicate the potential value of proinsulin for identification of RTR at increased risk for NODAT.

OBJECTIVE The creatinine excretion rate (CER) is inversely associated with mortality in the general and renal transplant population. The CER is a marker for muscle mass. It is unknown whether the CER is associated with outcome in diabetes. We therefore investigated whether the CER is a determinant of all-cause mortality in diabetic patients. RESEARCH DESIGN AND METHODS We used data from the combined Reduction of Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy Trial (IDNT) studies. A total of 1,872 patients (58% of the overall population) with type 2 diabetes and nephropathy with valid 24-h urinary creatinine excretion data were included. The primary end point of the analyses was all-cause mortality. RESULTS Mean age was 60 ± 8 years and median CER was 1,407 (total range 400–3,406) mg/day. Body surface area, hemoglobin, black race, and albuminuria were positive independent determinants of the CER, whereas female sex and age were inverse independent determinants of the CER. During a median follow-up of 36 (29–45) months, 300 patients died. In a Kaplan-Meier analysis of sex-stratified tertiles of the CER, risk for all-cause mortality increased with decreasing CER (P < 0.001). In a multivariable Cox regression analysis, lower CER (as a continuous variable) was independently associated with increased risk for all-cause mortality (hazard ratio 0.39 [95% CI 0.29–0.52], P < 0.001). Adjustment for potential collection errors did not materially change these associations. CONCLUSIONS Lower CER was strongly associated with increased all-cause mortality in patients with type 2 diabetes and nephropathy. As the CER can be considered a proxy for muscle mass, this puts renewed emphasis on physical condition and exercise in this population.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes. This work was supported by MARATO TV3 (081630), Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional–European Regions Development Funds (Red de Investigación Cardiovascular RD12/0042 [Programa HERACLES], Red RedIAPP RD12/0005, RD06/0018, PI081327, and PI1101801), Agency for Management of University and Research Grants (2014 SGR 240), Consortium for Biomedical Research in Epidemiology and Public Health, and Consortium for Biomedical Research in Obesity and Nutrition. M.G. was supported by the Instituto de Salud Carlos III– Fondo Europeo de Desarrollo Regional–European Regions Development Fund FEDER (FIS CP12/ 03287).

OBJECTIVE-The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors. RESULTS-During follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15-2.20), 1.41 (95% CI 1.14-1.74), and 1.48 (95% CI 1.10-2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1-1.54]) and all-cause mortality (0.4 [0.05-0.92]), but not for new-onset albuminuria. CONCLUSIONS-CT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality.

OBJECTIVE-Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events. RESULTS-The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9). CONCLUSIONS-In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina. Diabetes Care 35: 2201-2206, 2012

OBJECTIVE-Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.RESEARCH DESIGN AND METHODS-A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events.RESULTS-The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9).CONCLUSIONS-In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina. Diabetes Care 35: 2201-2206, 2012

OBJECTIVE To investigate whether intake of different types of meat is associated with circulating C-reactive protein (CRP) and risk of type 2 diabetes in a prospective cohort study. RESEARCH DESIGN AND METHODS Our analysis included 4,366 Dutch participants who did not have diabetes at baseline. During a median follow-up period of 12.4 years, 456 diabetes cases were confirmed. Intake of red meat, processed meat, and poultry was derived from a food frequency questionnaire, and their association with serum high-sensitivity CRP was examined cross-sectionally using linear regression models. Their association with risk of type 2 diabetes was examined using multivariate Cox proportional hazards model, including age, sex, family history of diabetes, and lifestyle and dietary factors. RESULTS An increment of 50 g of processed meat was associated with increased CRP concentration (ßprocessed meat = 0.12; P = 0.01), whereas intake of red meat and poultry was not. When comparing the highest to the lowest category of meat intake with respect to diabetes incidence, the adjusted relative risks were as follows: for red meat (1.42 [95% CI 1.06–1.91]), for processed meat (1.87 [1.26–2.78]), and for poultry (0.95 [0.74–1.22]). Additional analysis showed that the associations were not affected appreciably after inclusion of CRP into the model. After adjustment for BMI, however, the association for red meat attenuated to 1.18 (0.88–1.59). CONCLUSIONS Intake of processed meat is associated with higher risk of type 2 diabetes. It appears unlikely that CRP mediates this association

It is beyond doubt that patients with diabetes are at high risk of developing renal and cardiovascular disease. Both outcomes have significant clinical implications and are associated with high additional costs. Several traditional (blood pressure, HbA1c, cholesterol) and novel cardiovascular biomarkers (C-reactive protein, pro-brain natriuretic peptide) are at hand to identify those individuals who will develop end-stage renal or cardiovascular disease, as early as possible. The traditional biomarkers have been successfully applied in clinical practice and have proven their clinical usefulness. Renal biomarkers, in particular, albuminuria and estimated glomerular filtration rate (eGFR), have been added to the biomarker armamentarium. Both are indeed associated with renal and cardiovascular disease in individuals with diabetes and may be used to identify individuals at risk of long-term complications. Although identifying individuals at risk is important, even more important is the question whether we can lower this risk by changing renal biomarkers through pharmacological (or other) intervention. This overview describes the performance of albuminuria and eGFR in predicting renal and cardiovascular disease. In the second part, the relationship between treatment-induced changes in these two renal biomarkers and renal and cardiovascular outcome will be described. ### Albuminuria The relationship between albuminuria and renal and cardiovascular disease has been well established. Its association was first described in patients with type 1 diabetes (1,2). Several studies followed these initial reports and confirmed the significance of albuminuria in predicting long-term renal prognosis. Data from prospective trials showed that patients with type 2 diabetes appear to progress from micro- to macroalbuminuria to end-stage renal disease (ESRD), similar to the earlier reports of patients with type 1 diabetes. The Reduction in End Points in Non-Insulin Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan (RENAAL) showed that albuminuria is the most critical baseline predictor for ESRD (3). Similar data …

OBJECTIVE-This study compared the durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25: 75% insulin lispro protamine suspension/25% lispro) and once-daily insulin glargine, added to oral antihyperglycemic drugs in type 2 diabetes patients.RESEARCH DESIGN AND METHODS-During the initiation phase, patients were randomized to LM75/25 or glargine. After 6 months, patients with A1CRESULTS-Of 900 patients receiving LM75/25 and 918 patients receiving glargine who completed initiation, 473 and 419, respectively, had A1CCONCLUSIONS-A modestly longer durability of glycemic control was achieved with LM75/25 compared with glargine. Patients with lower baseline A1C levels were more likely to maintain the goal, supporting the concept of earlier insulin initiation.

OBJECTIVE-This study compared the durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25: 75% insulin lispro protamine suspension/25% lispro) and once-daily insulin glargine, added to oral antihyperglycemic drugs in type 2 diabetes patients. RESEARCH DESIGN AND METHODS-During the initiation phase, patients were randomized to LM75/25 or glargine. After 6 months, patients with A1C RESULTS-Of 900 patients receiving LM75/25 and 918 patients receiving glargine who completed initiation, 473 and 419, respectively, had A1C CONCLUSIONS-A modestly longer durability of glycemic control was achieved with LM75/25 compared with glargine. Patients with lower baseline A1C levels were more likely to maintain the goal, supporting the concept of earlier insulin initiation.

The use of A1C for the identification of persons with undiagnosed diabetes has been investigated for a number of years (1–3). A1C better reflects long-term glycemic exposure than current diagnostic tests based on point-in-time measures of fasting and postload blood glucose (4,5) and has improved test-retest reliability (6). In addition, A1C includes no requirement for fasting or for the oral glucose tolerance test's 2-h wait. These advantages should lead to increased identification and more timely treatment of persons with diabetes. Recently, an American Diabetes Association (ADA)-organized international expert committee recommended the adoption of the A1C assay for the diagnosis of diabetes at a cut point of 6.5% (7). This cut point was primarily derived from a review of studies that examined the association of A1C values with incident retinopathy, and some of the most influential data were obtained from recently published prospective studies. Retinopathy was chosen as the ultimate criterion because it is among the main complications of diabetes. Identification of the point on the A1C distribution most closely related to future retinopathy will identify persons in the greatest need of interventions for the prevention of diabetes complications. In addition to utility and convenience, A1C could help identify persons at increased risk of developing diabetes. This is an important public health priority since a structured lifestyle program or the drug metformin can reduce the incidence of diabetes by at least 50 and 30%, respectively (8). Ideally, selection of diagnostic cut points for pre-diabetes would be based on evidence that intervention, when applied to the high-risk group of interest, results not only in the prevention of diabetes but also later complications. However, currently there are no trials that can provide data to determine the ideal method for defining cut points. In the absence of such data, expert committees had to rely on information about the shape of risk curves for complications such as retinopathy. Previous expert committees assembled to address this issue have noted that there is no clear difference in retinopathy risk between different levels of impaired glucose tolerance (7). We are unaware of published prospective studies of adequate sample size or duration that have followed people in various pre-diabetic categories across the full span of time until complications developed. In the absence of informative trials (as well as prospective studies), the studies that measure A1C at baseline and incident diabetes may provide the definitions of high-risk states. To better define A1C ranges that might identify persons who would benefit from interventions to prevent or delay type 2 diabetes, we carried out a systematic review of published prospective studies that have examined the relationship of A1C to future diabetes incidence.

OBJECTIVE - Several Studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort.RESEARCH DESIGN AND METHODS - in 1998 and 1999,1,353 patients With type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care 0 (ZODIAC) study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using Standardized Mortality ratios (SMRs), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazards model, taking possible confounders into account.RESULTS - Median follow-up time was 9.6 years, average age at baseline was 68 years, and average A1C was 7.5%. Of the patients, 570 died, of which 122 died of malignancies. The SMR for cancer mortality was 1.47 (95% CI 1.22-1.76). In patients taking metformin compared with patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95% Cl 0.23-0.80), and the HR With every increase of I g of metformin was 0.58 (95% CI 0.36-093),CONCLUSIONS - in general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality compared with nonuse of metformin. Although the design cannot provide a conclusion about causality, our results suggest a protective effect of metformin on cancer mortality.

OBJECTIVE - To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes. RESEARCH DESIGN AND METHODS - This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR-based regimen (target A1C RESULTS - There was no interaction between the effects of routine blood pressure lowering and intensive glucose control for any of the prespecified clinical Outcomes (all P > 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% Cl 12-50%, P = 0.005), new onset of macroalbuminuria by 54% (35-68%, P

OBJECTIVE—We examined the prevalences of diagnosed diabetes, and undiagnosed diabetes and pre-diabetes using fasting and 2-h oral glucose tolerance test values, in the U.S. during 2005–2006. We then compared the prevalences of these conditions with those in 1988–1994. RESEARCH DESIGN AND METHODS—In 2005–2006, the National Health and Nutrition Examination Survey included a probability sample of 7,267 people aged ≥12 years. Participants were classified according to glycemic status by interview for diagnosed diabetes and by fasting and 2-h glucoses measured in subsamples. RESULTS—In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ∼40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had diabetes or pre-diabetes. Compared with non-Hispanic whites, age- and sex-standardized prevalence of diagnosed diabetes was approximately twice as high in non-Hispanic blacks (P < 0.0001) and Mexican Americans (P = 0.0001), whereas undiagnosed diabetes was not higher. Crude prevalence of diagnosed diabetes in people aged ≥20 years rose from 5.1% in 1988–1994 to 7.7% in 2005–2006 (P = 0.0001); this was significant after accounting for differences in age and sex, particularly in non-Hispanic blacks. Prevalences of undiagnosed diabetes and pre-diabetes were generally stable, although the proportion of total diabetes that was undiagnosed decreased in Mexican Americans. CONCLUSIONS—Over 40% of people aged ≥20 years have hyperglycemic conditions, and prevalence is higher in minorities. Diagnosed diabetes has increased over time, but other conditions have been relatively stable. Diabetes and its complications remain major causes of morbidity and mortality in the U.S. (1). Estimated economic costs of diabetes in medical expenditures and lost productivity total $174 billion in the U.S. in 2007 (2). In 1999–2002, the crude prevalence of diabetes (diagnosed and undiagnosed) in the U.S. was 9.3%, of which 30% was undiagnosed based on fasting plasma glucose (FPG) (3). A further 26% had impaired fasting glucose (IFG). IFG increases the risk of diabetes (4), and both undiagnosed diabetes and IFG are associated with diabetes complications and risk factors (4,5). These prevalence data came from the National Health and Nutrition Examination Survey (NHANES), the only national survey that captures information on diabetes and pre-diabetes from an interview and FPG. In 2005–2006, an oral glucose tolerance test (OGTT) was added to NHANES, which had not been performed since NHANES 1988–1994. Whereas elevated FPG is determined more by impaired hepatic insulin resistance, elevated 2-h plasma glucose from an OGTT is determined predominantly by peripheral insulin resistance (4,6). The OGTT aids in detecting the total burden of diabetes and also impaired glucose tolerance (IGT). Two-hour plasma glucose values are more sensitive in the elderly (7), an increasing proportion of the U.S. population. IGT also predicts diabetes and is more commonly associated with cardiovascular disease risk factors and events than IFG (4,8). In this report, we analyze the prevalence of diagnosed diabetes, undiagnosed diabetes based on fasting and 2-h plasma glucose from an OGTT, and pre-diabetes (IFG or IGT) in people aged ≥12 years using data from NHANES 2005–2006. Results are presented by age, sex, and race/ethnicity. We compare these estimates with those from NHANES 1988–1994. The addition of the OGTT also allowed assessment of the agreement between diagnostic categories defined by fasting and 2-h plasma glucose. Although this was examined in NHANES 1988–1994 in those aged 40–74 years (9), a reexamination is appropriate given 1) the measurements in a wider age range in NHANES 2005–2006, 2) the change in criteria for IFG (lowered from 110 to 100 mg/dl) since that report (8), and 3) the rising prevalence of glucose abnormalities (3) and obesity (10).

OBJECTIVE—Women with diabetes have a high incidence and complication rate of urinary tract infections (UTIs). Our aims were to compare current treatment strategies with respect to recurrence rates in women with diabetes with those without diabetes. RESEARCH DESIGN AND METHODS—We used a Dutch registration database containing pharmacy dispensing data. A total of 10,366 women with diabetes (17.5% premenopausal) (aged ≤55 years) and 200,258 women without diabetes (68% premenopausal) who received a first course of trimethoprim, nitrofurantoin, fosfomycin, or norfloxacin between January 1999 and January 2006 were included. We compared short (≤5 days) with long (>5 days) prescriptions and norfloxacin with trimethoprim, nitrofurantoin, and fosfomycin. A recurrence was defined as a second prescription for one of the above-mentioned agents or a first with amoxicillin (clavulanic acid), fluoroquinolones, or trimethoprim/sulfamethoxazole between 6 and 30 days after inclusion. RESULTS—Premenopausal women with diabetes more often received a long (26.5 vs. 19.2%; P < 0.001) treatment with norfloxacin (10.7 vs. 6.2%; P < 0.001) but still had a higher recurrence rate (16.1 vs. 12.2%; P = 0.003) compared with those without diabetes. Similarly, postmenopausal women with diabetes more often received a longer (32.8 vs. 28.8%; P < 0.001) treatment with norfloxacin (15.2 vs. 12.7%; P < 0.001) but had a higher recurrence rate (19.1 vs. 16.4%; P < 0.001) compared with those without diabetes. CONCLUSIONS—Despite the fact that patients with diabetes more often received longer and more potent initial treatment than patients without diabetes, pre- and postmenopausal women with diabetes more often had recurrences of their UTIs.

OBJECTIVE - The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS- Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients. RESULTS - The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score >= 20) was 645 (40.2% [95% CI 37.8-42.6]); of these, 35 (2.2% [1.6-3.01) had severe diabetic retinopathy (ETDRS score >= 50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5. 1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P

OBJECTIVE - The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial.RESEARCH DESIGN AND METHODS- Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients.RESULTS - The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score >= 20) was 645 (40.2% [95% CI 37.8-42.6]); of these, 35 (2.2% [1.6-3.01) had severe diabetic retinopathy (ETDRS score >= 50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5. 1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P CONCLUSIONS - Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups.

OBJECTIVE - Skin auto fluorescence is a noninvasive measure of the level of tissue accumulation of advanced glycation end products, representing cumulative glycemic and oxidative stress. Recent studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as the predictive value of skin autofluorescence for total and cardiovascular mortality in type 2 diabetes. Our aim was to investigate the predictive value of skin autofluorescence for the development of microvascular complications in type 2 diabetes.RESEARCH DESIGN AND METHODS - At baseline, skin autofluorescence of 973 type 2 diabetic patients with well-controlled diabetes was noninvasively measured with an autofluorescence reader. The aggregate clinical outcome was defined as the development of any diabetes-associated microvascular complication of 881 surviving patients, which was assesse at baseline and at the end of follow-up. Single end points were the development of diabetes-sassociated retinopathy, neuropathy, and (micro)albuminuria.RESULTS - After a mean follow-up period of 3.1 years, baseline skin autofluorescence was significantly higher in patients who developed any microvascular complication, neuropathy, or (micro) albuminuria but not in those who developed retinopathy. Multivariate analyses showed skin auto fluorescence as a predictor for development of any microvascular complication along with AlC, for development of neuropathy along with smoking, and for development of (micro)albuminuria together with sex, AlC, and diabetes duration. Skin autofluorescence did not have predictive value for the development of retinopathy, albeit diabetes duration did.CONCLUSIONS - Our study is the first observation of skin autofluorescence measurement as an independent predictor of development of microvascular complications in type 2 diabetes.

OBJECTIVE - Skin auto fluorescence is a noninvasive measure of the level of tissue accumulation of advanced glycation end products, representing cumulative glycemic and oxidative stress. Recent studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as the predictive value of skin autofluorescence for total and cardiovascular mortality in type 2 diabetes. Our aim was to investigate the predictive value of skin autofluorescence for the development of microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS - At baseline, skin autofluorescence of 973 type 2 diabetic patients with well-controlled diabetes was noninvasively measured with an autofluorescence reader. The aggregate clinical outcome was defined as the development of any diabetes-associated microvascular complication of 881 surviving patients, which was assesse at baseline and at the end of follow-up. Single end points were the development of diabetes-sassociated retinopathy, neuropathy, and (micro)albuminuria. RESULTS - After a mean follow-up period of 3.1 years, baseline skin autofluorescence was significantly higher in patients who developed any microvascular complication, neuropathy, or (micro) albuminuria but not in those who developed retinopathy. Multivariate analyses showed skin auto fluorescence as a predictor for development of any microvascular complication along with AlC, for development of neuropathy along with smoking, and for development of (micro)albuminuria together with sex, AlC, and diabetes duration. Skin autofluorescence did not have predictive value for the development of retinopathy, albeit diabetes duration did. CONCLUSIONS - Our study is the first observation of skin autofluorescence measurement as an independent predictor of development of microvascular complications in type 2 diabetes.

OBJECTIVE—The purpose of this study was to examine risk factors for mortality in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Baseline risk factors were measured in the EURODIAB Prospective Cohort Study with 2,787 type 1 diabetic patients (51% men and 49% women) recruited from 16 European countries. Mortality data were collected during a 7-year follow-up. RESULTS—There was an annual mortality rate of 5 per 1,000 person-years in patients with type 1 diabetes (mean age at baseline 33 years, range 15–61 years); of the total 2,787 subjects, 102 died. The final multivariable model contained age at baseline (standardized hazard ratio 1.78 [95% CI 1.44–2.20]), A1C (1.18 [0.95–1.46]), waist-to-hip ratio (WHR) (1.32 [1.14–1.52]), pulse pressure (1.33 [1.13–1.58]), and non-HDL cholesterol (1.33 [1.12–1.60]) as risk factors for all-cause mortality. Macroalbuminuria (2.39 [1.19–4.78]) and peripheral (1.88 [1.06–3.35]) and autonomic neuropathy (2.40 [1.32–4.36]) were the most important risk markers for mortality. Similar risk factors were found for all-cause, non-cardiovascular disease (CVD), unknown-cause, and CVD mortality. CONCLUSIONS—Important risk factors for the increased total and non-CVD mortality in type 1 diabetic patients are age, WHR, pulse pressure, and non-HDL cholesterol. Microvascular complications from macroalbuminuria and peripheral and autonomic neuropathy are strong risk markers for future mortality exceeding the effect of the traditional risk factors

OBJECTIVE - Pharmacoepidemiological studies have shown an increased prevalence of diabetes in patients with schizophrenia. To address this issue, we decided to assess glucose metabolism in a population of patients With schizophrenia or schizoaffective disorder.RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) were performed in 200 unselected in- and outpatients. Insulin sensitivity and beta-cell function were assessed using the homeostasis model assessment (HOMA) indexes and 30-min glucose and insulin levels.RESULTS - The mainly Western European (87.7%) study population had a mean age of 40.8 years, was 70% male, and had a mean fasting glucose of 5.1 mmol/l and a mean fasting insulin of 1.4.8 mU/l. Hvperglycemia was present in 7% of the population: 1.5% with impaired fasting glucose and 5.5% with impaired glucose tolerance. The prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was newly diagnosed. Compared with a 1.5% prevalence of diabetes in the age-matched general Dutch population, the prevalence of identified cases was significantly increased in the Study population. Comparable figures on the prevalence of hyperglycemia in the general population are not available. Insulin resistance was increased in the stud), population as a whole (HOMA of insulin resistance: 3.1-3.5), irrespective of the use of antipsychotic medication and, if used, irrespective of its type (typical or atypical). No indication of beta-cell defect was found, whereas a nonsignificant increased insulin resistance was found With antipsychotic medication.CONCLUSIONS - OGTTs in 200 mainly Caucasian patients with schizophrenia or schizoaffective disorder, mean age 41 years, showed that 7% suffered from hyperglycemia and 14.5% from diabetes. The prevalence of diabetes was significantly increased compared with the general population. No differential effect of antipsychotic monotherapy in diabetogenic effects was found. Therefore, a modification of the consensus statement on antipsychotic drugs, obesity, and diabetes is proposed, i.e., measurement of fasting glucose in all patients with schizophrenia, irrespective of prescribed antipsychotic drug.

OBJECTIVE - Pharmacoepidemiological studies have shown an increased prevalence of diabetes in patients with schizophrenia. To address this issue, we decided to assess glucose metabolism in a population of patients With schizophrenia or schizoaffective disorder. RESEARCH DESIGN AND METHODS - Oral glucose tolerance tests (OGTTs) were performed in 200 unselected in- and outpatients. Insulin sensitivity and beta-cell function were assessed using the homeostasis model assessment (HOMA) indexes and 30-min glucose and insulin levels. RESULTS - The mainly Western European (87.7%) study population had a mean age of 40.8 years, was 70% male, and had a mean fasting glucose of 5.1 mmol/l and a mean fasting insulin of 1.4.8 mU/l. Hvperglycemia was present in 7% of the population: 1.5% with impaired fasting glucose and 5.5% with impaired glucose tolerance. The prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was newly diagnosed. Compared with a 1.5% prevalence of diabetes in the age-matched general Dutch population, the prevalence of identified cases was significantly increased in the Study population. Comparable figures on the prevalence of hyperglycemia in the general population are not available. Insulin resistance was increased in the stud), population as a whole (HOMA of insulin resistance: 3.1-3.5), irrespective of the use of antipsychotic medication and, if used, irrespective of its type (typical or atypical). No indication of beta-cell defect was found, whereas a nonsignificant increased insulin resistance was found With antipsychotic medication. CONCLUSIONS - OGTTs in 200 mainly Caucasian patients with schizophrenia or schizoaffective disorder, mean age 41 years, showed that 7% suffered from hyperglycemia and 14.5% from diabetes. The prevalence of diabetes was significantly increased compared with the general population. No differential effect of antipsychotic monotherapy in diabetogenic effects was found. Therefore, a modification of the consensus statement on antipsychotic drugs, obesity, and diabetes is proposed, i.e., measurement of fasting glucose in all patients with schizophrenia, irrespective of prescribed antipsychotic drug.

OBJECTIVE - Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific populations of patients with type 2 diabetes. The aim of this study was to determine the effect of chromium treatment on glycemic Control in -,I Western population of insulin-dependent patients with type 2 diabetes.RESEARCH DESIGN AND METHODS - In this 6-month double-blind study, patients with an HbA(1c) (A1C) > 8% and insulin requirements of > 50 units/day were randomly assigned to receive treatment with placebo or 500 or 1,000 mu g chromium daily in the form of chromium picolinate. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, and insulin requirements.RESULTS - in this per-protocol analysis (n = 46), the decrease in A1C was approximately equal across the three groups (0.4%). All Patients had a BMI > 25 kg/m(2). No differences were found in the secondary end points. We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile.CONCLUSIONS - There is no evidence that high-dose chromium treatment is effective in obese Western patients With type 2 diabetes.

OBJECTIVE—To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K. RESEARCH DESIGN AND METHODS—Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.K. population. Incident major CVD events, comprising myocardial infarction, acute coronary heart disease death, coronary revascularizations, or stroke, were captured for the period 1992–1999. RESULTS—The hazard ratio (HR) for major CVD was 3.6 (95% CI 2.9–4.5) in type 1 diabetic men compared with those without diabetes and 7.7 (5.5–10.7) in women. Increased HRs were found for acute coronary events (3.0 and 7.6 in type 1 diabetic men and women, respectively, versus nondiabetic subjects), coronary revascularizations (5.0 in men, 16.8 in women), and for stroke (3.7 in men, 4.8 in women). Type 1 diabetic men aged 45–55 years had an absolute CVD risk similar to that of men in the general population 10–15 years older, with an even greater difference in women. CONCLUSIONS—Despite advances in care, these data show that absolute and relative risks of CVD remain extremely high in patients with type 1 diabetes. Women with type 1 diabetes continue to experience greater relative risks of CVD than men compared with those without diabetes.

OBJECTIVE - This study aimed to investigate the relation between alcohol consumption and type 2 diabetes among older women.RESEARCH DESIGN AND METHODS- Between 1993 and 1997, 16,330 women aged 49-70 years and free from diabetes were enrolled in one of the Dutch Prospect-EPIC ( European Prospective Study Into Cancer and Nutrition) cohorts and followed for 6.2 years (range 0.1-10.1). At enrollment, women filled in questionnaires and blood samples were collected.RESULTS - During follow-up, 760 cases of type 2 diabetes were documented. A linear inverse association (P = 0.007) between alcohol consumption and type 2 diabetes risk was observed, adjusting for potential confounders. Compared with abstainers, the hazard ratio for type 2 diabetes was 0.86 (95% CI 0.66-1.12) for women consuming 5-30 g alcohol per week, 0.66 (0.48-0.91) for 30-70 g per week, 0.91 (0.67-1.24) for 70-140 g per week, 0.64 (0.44-0.93) for 140-210 g per week, and 0.69 (0.47-1.02) for > 210 g alcohol per week. Beverage type did not influence this association. Lifetime alcohol consumption was associated with type 2 diabetes in a U-shaped Fashion.CONCLUSIONS - our findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand this to a population of older women.

OBJECTIVE—This study aimed to investigate the relation between alcohol consumption and type 2 diabetes among older women. RESEARCH DESIGN AND METHODS—Between 1993 and 1997, 16,330 women aged 49–70 years and free from diabetes were enrolled in one of the Dutch Prospect-EPIC (European Prospective Study Into Cancer and Nutrition) cohorts and followed for 6.2 years (range 0.1–10.1). At enrollment, women filled in questionnaires and blood samples were collected. RESULTS—During follow-up, 760 cases of type 2 diabetes were documented. A linear inverse association (P = 0.007) between alcohol consumption and type 2 diabetes risk was observed, adjusting for potential confounders. Compared with abstainers, the hazard ratio for type 2 diabetes was 0.86 (95% CI 0.66–1.12) for women consuming 5–30 g alcohol per week, 0.66 (0.48–0.91) for 30–70 g per week, 0.91 (0.67–1.24) for 70–140 g per week, 0.64 (0.44–0.93) for 140–210 g per week, and 0.69 (0.47–1.02) for >210 g alcohol per week. Beverage type did not influence this association. Lifetime alcohol consumption was associated with type 2 diabetes in a U-shaped fashion. CONCLUSIONS—Our findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand this to a population of older women.

OBJECTIVE - This study aimed to investigate the relation between alcohol consumption and type 2 diabetes among older women. RESEARCH DESIGN AND METHODS- Between 1993 and 1997, 16,330 women aged 49-70 years and free from diabetes were enrolled in one of the Dutch Prospect-EPIC ( European Prospective Study Into Cancer and Nutrition) cohorts and followed for 6.2 years (range 0.1-10.1). At enrollment, women filled in questionnaires and blood samples were collected. RESULTS - During follow-up, 760 cases of type 2 diabetes were documented. A linear inverse association (P = 0.007) between alcohol consumption and type 2 diabetes risk was observed, adjusting for potential confounders. Compared with abstainers, the hazard ratio for type 2 diabetes was 0.86 (95% CI 0.66-1.12) for women consuming 5-30 g alcohol per week, 0.66 (0.48-0.91) for 30-70 g per week, 0.91 (0.67-1.24) for 70-140 g per week, 0.64 (0.44-0.93) for 140-210 g per week, and 0.69 (0.47-1.02) for > 210 g alcohol per week. Beverage type did not influence this association. Lifetime alcohol consumption was associated with type 2 diabetes in a U-shaped Fashion. CONCLUSIONS - our findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand this to a population of older women.

OBJECTIVE - To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose >= 7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable. RESULTS - Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P

OBJECTIVE - To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes.RESEARCH DESIGN AND METHODS - We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose >= 7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable.RESULTS - Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P CONCLUSIONS - UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP.

OBJECTIVE—To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS—We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose ≥7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable. RESULTS—Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P < 0.001 for all variables). In a univariate model, the odds ratio (OR) for UAE was 1.59 (95% CI 1.42–1.79). In our full model, adjusted for age, sex, number of criteria of metabolic syndrome, and other known risk factors for the development of type 2 diabetes (including fasting insulin), the association between UAE and type 2 diabetes remained significant (OR 1.53, 95% CI 1.25–1.88, P < 0.001). There was a significant interaction between UAE and CRP (P = 0.002). After CRP was stratified into tertiles, the ORs for the association between baseline UAE and the development of type 2 diabetes were 2.2 (1.47–3.3), 1.33 (0.96–1.84), and 1.04 (0.83–1.31) for the lowest to highest tertiles, respectively. CONCLUSIONS—UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP.

OBJECTIVE—To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve. RESULTS—Overall, 1,377 individuals aged between 55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a marked variation according to glucose metabolism categories, as follows: 8.7 ± 3.0 in normoglycemic individuals, 9.5 ± 3.1 in individuals with impaired fasting glucose, 9.9 ± 3.3 in individuals with IGT, and 12.0 ± 3.5 in individuals with type 2 diabetes. The receiver-operating characteristic curve showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity 45%. The use of the DRS as an initial screening instrument, followed by the measurement of fasting blood glucose in individuals with a score ≥9 and by the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l, would lead to the identification of 83% of the case subjects with type 2 diabetes and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample and a fasting blood glucose in 64%. CONCLUSIONS—The DRS can represent a valid inexpensive instrument for opportunistic screening and a useful alternative to indiscriminate fasting blood glucose measurement, not readily available in general practice.

OBJECTIVE - To assess the quality of hypertension care in patients with type 2 diabetes in general practice and identify physician, organizational, and patient factors associated with suboptimal care.RESEARCH DESIGN AND METHODS - Data from 895 randomly selected diabetic patients were extracted from the electronic medical records of 95 general practitioners. Physician and organizational characteristics were collected with a questionnaire. We conducted a multi-level analysis to identify associations with blood pressure registration, hypertension treatment, and achievement of target blood pressure levels.RESULTS - For 652 patients (73%), a blood pressure measurement was recorded in the last year. Of these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595 patients were classified as having hypertension, of whom 192 received no treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other anti hypertensives. Patients visiting a diabetes facility, referred to a specialist, with a female general practitioner, or with a general practitioner with less than or equal to10 years work experience had better recordings of their blood pressure. Sub optimal treatment was higher in older patients and smoking patients. Treatment was better in patients with coronary comorbidity, hyperlipidemia, or those referred to a specialist. Not achieving the blood pressure target was related to older age of the patients.CONCLUSIONS - Hypertension management of type 2 diabetic patients in primary care is suboptimal. Characteristics of general practitioners as well as additional care provided by a diabetes facility or a specialist are associated with better processes of care, but blood pressure outcomes are not as clearly related to these factors.

OBJECTIVE—The goal of the study was to examine risk factors in the prediction of coronary heart disease (CHD) and differences in men and women in the EURODIAB Prospective Complications Study. RESEARCH DESIGN AND METHODS—Baseline risk factors and CHD at follow-up were assessed in 2,329 type 1 diabetic patients without prior CHD. CHD was defined as physician-diagnosed myocardial infarction, angina pectoris, coronary artery bypass graft surgery, and/or Minnesota-coded ischemic electrocardiograms or fatal CHD. RESULTS—There were 151 patients who developed CHD, and the 7-year incidence rate was 8.0 (per 1,000 person-years) in men and 10.2 in women. After adjustment for age and/or duration of diabetes, the following risk factors were related to CHD in men: age, GHb, waist-to-hip ratio (WHR), HDL cholesterol, smoking, albumin excretion rate (AER), and autonomic neuropathy. The following risk factors were related to CHD in women: age, systolic blood pressure (BP), fasting triglycerides, AER, and retinopathy. Multivariate standardized Cox proportional hazards models showed that age (hazard ratio 1.5), AER (1.3 in men and 1.6 in women), WHR (1.3 in men), smoking (1.5 in men), fasting triglycerides (1.3 in women) or HDL cholesterol (0.74 in women), and systolic BP (1.3 in women) were predictors of CHD. CONCLUSIONS—This study supports the evidence for a strong predictive role of baseline albuminuria in the pathogenesis of CHD in type 1 diabetes. Furthermore, sex-specific risk factors such as systolic BP, fasting triglycerides (or HDL cholesterol), and WHR were found to be important in the development of CHD

OBJECTIVE - To assess the quality of hypertension care in patients with type 2 diabetes in general practice and identify physician, organizational, and patient factors associated with suboptimal care. RESEARCH DESIGN AND METHODS - Data from 895 randomly selected diabetic patients were extracted from the electronic medical records of 95 general practitioners. Physician and organizational characteristics were collected with a questionnaire. We conducted a multi-level analysis to identify associations with blood pressure registration, hypertension treatment, and achievement of target blood pressure levels. RESULTS - For 652 patients (73%), a blood pressure measurement was recorded in the last year. Of these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595 patients were classified as having hypertension, of whom 192 received no treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other anti hypertensives. Patients visiting a diabetes facility, referred to a specialist, with a female general practitioner, or with a general practitioner with less than or equal to10 years work experience had better recordings of their blood pressure. Sub optimal treatment was higher in older patients and smoking patients. Treatment was better in patients with coronary comorbidity, hyperlipidemia, or those referred to a specialist. Not achieving the blood pressure target was related to older age of the patients. CONCLUSIONS - Hypertension management of type 2 diabetic patients in primary care is suboptimal. Characteristics of general practitioners as well as additional care provided by a diabetes facility or a specialist are associated with better processes of care, but blood pressure outcomes are not as clearly related to these factors.

OBJECTIVE - The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes.RESEARCH DESIGN AND METHODS - We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes.RESULTS - CETP TaqlB and A-629C polymorphisms were tightly concordant (P CONCLUSIONS - in conclusion, the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile, including low HDL, and they respond better to statin therapy. These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy.

OBJECTIVE - The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes. RESEARCH DESIGN AND METHODS - We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes. RESULTS - CETP TaqlB and A-629C polymorphisms were tightly concordant (P

OBJECTIVE - To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from I year before until 6 years after the start of oral antidiabetic therapy.RESEARCH DESIGN AND METHODS - In this cohort study, 2,584 patients With type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch Cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997, Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies,RESULTS - Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects, Differences between patients with type 2 diabetes and nondiabetic subjects lessened from I year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks lot, diuretics, beta -blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were similar to 50% in the years close to the start of oral antidiabetic treatment and decreased to similar to 33% in the following),cars.CONCLUSIONS - Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta -blockers, whereas cardiovascular hospitalizations First decreased and then stabilized.

OBJECTIVE - To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from I year before until 6 years after the start of oral antidiabetic therapy. RESEARCH DESIGN AND METHODS - In this cohort study, 2,584 patients With type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch Cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997, Nondiabetic subjects were 1:1-matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies, RESULTS - Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23-1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33-1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects, Differences between patients with type 2 diabetes and nondiabetic subjects lessened from I year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks lot, diuretics, beta -blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were similar to 50% in the years close to the start of oral antidiabetic treatment and decreased to similar to 33% in the following),cars. CONCLUSIONS - Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially beta -blockers, whereas cardiovascular hospitalizations First decreased and then stabilized.

OBJECTIVE - Women with diabetes have urinary tract infections (UTIs) more often than women without diabetes. The aim of the present multicenter study was to evaluate which clinical characteristics are associated with the development of a symptomatic UTI during an 18-month follow-up period. RESEARCH DESIGN AND METHODS - Patients with either type 1 or type 2 diabetes who were between 18 and 75 years of age were included. Follow-up results were available for 589 of the 636 women included in this study. All patients were interviewed, their medical history was noted, and at least one uncontaminated urine culture was collected at the moment of study entry. RESULTS - Of the 589 women, 115 (20%) developed a symptomatic UTI, 96 (83%) of whom were prescribed antimicrobial therapy. A total of 34 women (14%) with type 1 diabetes developed a UTI. The most important risk factor for these women was sexual intercourse during the week before entry into the study (44% without vs. 53% with sexual intercourse, relative risk [RR] = 3.0, P = 0.01). A total of 81 (23%) women with type 2 diabetes developed a UTI. The most important risk factor for these women was the presence of asymptomatic bacteriuria (ASB) at baseline (25% without vs. 42% with ASB, RR = 1.65, P = 0.04). CONCLUSIONS - Risk factors for developing a UTI are the presence of ASB for women with type 2 diabetes and sexual intercourse during the week before entry into the study for women with type 1 diabetes.