Abstract Aims/Introduction Data of nationwide glycemic control and hypoglycemic treatment patterns in newly diagnosed type 2 diabetes patients in China are absent. The aim of this study was to assess the evolution of treatment patterns for newly diagnosed type 2 diabetes patients and the clinical outcomes during 12‐month follow up. Materials and Methods This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes for <6 months were enrolled. Glycated hemoglobin A1c (HbA1c) levels and hypoglycemic treatment patterns were collected at baseline and at every 3 months of follow up. Results A total of 79 hospitals were recruited, consisting of 5,770 participants. The mean HbA1c was 8.4 ± 2.5% at baseline, and decreased to 6.7 ± 1.2% at 12 months with 68.5% of patients achieving HbA1c <7%. At baseline, 44.6% of the patients were without hypoglycemic medications, 37.7% had oral hypoglycemic agents and 17.7% received insulin treatment. Determinants of change in HbA1c were treatment patterns, comorbidities, baseline characteristics such as obesity and smoking, regions, and tiers of hospitals. Associated factors with treatment alterations were time of follow up, treatment patterns, patient‐reported reasons such as the economic factors and poor efficacy. Conclusions In newly diagnosed type 2 diabetes patients, compared with patients without medications, patients with one oral hypoglycemic agent had higher possibilities of reaching glycemic control, whereas patients using insulin had lower possibilities of reaching the target. Factors associated with change in HbA1c and treatment alterations were also revealed.

AbstractAims/IntroductionThere are substantial differences in genes, diet, culture and environment between the northern and southern Chinese populations, which might influence treatment strategy and screening policy. We studied the differences in type 2 diabetes and diabetic complications between northern and southern China.Materials and MethodsWe carried out a cross‐sectional survey using data from the China Cardiometabolic Registries on blood pressure, blood lipids and blood glucose in 25,398 Chinese type 2 diabetes patients. Macrovascular, microvascular and other complications were collected by self‐report or medical records, and then divided into the northern and southern groups by the boundary of the Yangtze River.ResultsNorthern patients were younger, and had heavier weight, greater body mass index and waist circumference, higher blood pressure, higher total cholesterol, higher low‐density lipoprotein cholesterol, and higher hemoglobin A1C. The prevalence of cardiovascular, cerebrovascular and macrovascular complications were 1.76‐fold, 1.24‐fold and 1.47‐fold more in northern than that in southern Chinese patients. In addition, the prevalence of diabetic nephropathy, retinopathy, neuropathy and microvascular complications in northern Chinese patients also increased. When stratified by age, the difference in both cardiovascular disease and ischemic stroke morbidity became significant, even in the 35–44 years age group.ConclusionsMore macrovascular and microvascular complications were found in northern compared with southern patients, and the largest difference also appeared in the younger age groups <55 years, which might be meaningful to a screening and treatment strategy according to geographic differences.

Background The efficacy of basal insulin (BI) for adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) has been well documented by randomized clinical trials. This post hoc analysis of the Observational Registry of Basal Insulin Treatment (ORBIT) study was performed to explore the 6-month dose of BI used in insulin-naive T2DM patients achieving HbA1c target (<7%) and determine the patient characteristics that affect the 6-month dose of BI in the setting of real-world clinics in China. Methods This multicenter observational registry screened 19 894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) in China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target were analyzed. Patient characteristics including age, body weight, fasting plasma glucose (FPG), use of OADs, insulin (type and dose), and glycemic control were recorded at baseline and 6-month follow-ups. Results The 6-month dose of BI needed for effective glycemic control was 0.20 +/- 0.08 U/kg/day. High body mass index, high FPG, young age, longer duration of diabetes or OAD treatment, a greater number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI at 6 months. Conclusions This post hoc analysis of the ORBIT registry provides key information on the 6-month dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, it identified crucial patient characteristics that are significant determinants of the dose of BI in a real-world setting.

Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered at www.clinicaltrials.gov (NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.

Aim. To investigate the metabolic profiles of newly diagnosed type 2 diabetes (NEW2D) in Chinese older adults (≥65 years) and assess the proportion of patients who achieved the targeted goals of blood glucose, blood pressure, and blood lipid. Methods. NEW2D study was an observational, longitudinal, prospective cohort study involving patients who were diagnosed with type 2 diabetes (T2D) within the past 6 months and had a follow-up of 12 months. Participants were divided into younger NEW2D group (aged 20-65 years old) and older NEW2D group (aged ≥65 years old) according to age of diabetes onset. The baseline metabolic profiles were compared and the proportion of patients achieving adequate control of blood glucose, blood pressure, and blood lipids in reference to target goals were assessed during treatment. Results. The older NEW2D (n=1362) had a lower BMI, HbA1c%, diastolic blood pressure, triglyceride, low-density lipoprotein cholesterol (LDL-C), and total cholesterol, higher systolic blood pressure, and high-density lipoprotein cholesterol levels at baseline. 47.8%, 66.7%, and 39.4% reached the target of HbA1c<7.0%, BP<140/90 mmHg, and LDL−C<2.6 mmol/L, respectively. After 12 months, the proportion achieving above three targets increased to 70.2%, 76.1%, and 47.5%, respectively. The proportions of patients achieving three combined therapeutic targets doubled from 13.5% to 26.7%. Conclusion. The older NEW2D patients have special metabolic profiles compared with younger patients. The control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes.

目的:初步评价国产精蛋白锌重组赖脯胰岛素混合注射液(25R)治疗糖尿病的有效性和安全性.方法:本研究为多中心、随机、开放和阳性药物[进口精蛋白锌重组赖脯胰岛素混合注射液(25R)]平行对照的Ⅲ期临床试验,包括2周的导入期和12周的治疗期.在15个研究中心预计入选514例糖尿病患者,以3:1的比例随机分配至国产组(386例)和进口组(128例)接受治疗.比较2组患者的糖化血红蛋白(HbA1c)、空腹血糖(FPG)及餐后2 h血糖(2 hPG)水平和低血糖事件发生情况.结果:与基线水平比较,治疗12周后国产组、进口组患者的HbA1c水平分别降低0.96％、0.82％,FPG水平分别降低1.74、1.94 mmol/L,2 hPG水平分别降低4.43、4.04 mmol/L,两组患者治疗前后上述指标水平的差异均有统计学意义(P<0.05);但两组间比较,差异均无统计学意义(P>0.05).国产组、进口组患者低血糖事件发生率分别为32.29％(124/384)、35.71％(45/126),不良事件发生率分别为27.34％(105/384)、23.02％(29/126),差异均无统计学意义(P>0.05).结论:国产精蛋白锌重组赖脯胰岛素混合注射液(25R)治疗糖尿病的有效性非劣效于进口精蛋白锌重组赖脯胰岛素混合注射液(25R),且具有良好的安全性.

AimTo assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy‐naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%‐12.0%).Research Design and MethodsIn this multicentre, double‐blind, active‐controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24.ResultsData from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m2; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (−3.0%) than with saxagliptin plus placebo (−2.1%; P < .001) or metformin plus placebo (−2.8%; P = .034). Changes in mean fasting plasma glucose, 120‐minute postprandial glucose, and 180‐minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common.ConclusionsSaxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment‐naïve Chinese patients with type 2 diabetes, and was well tolerated.

BackgroundLimited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN). MethodsAn 11-week double-blind placebo-controlled trial was performed in Chinese pDPN patients randomized (1 : 1) to 300 mg/day pregabalin or placebo. The primary outcome was change from baseline to endpoint in mean pain score (MPS; 0, no pain; 10, worst possible pain; using the mean of the last seven daily pain scores). Secondary outcomes included weekly MPS and responder status (MPS reduced by 30% or 50% vs baseline). Subgroup analysis assessed patients with severe (7) baseline MPS. Adverse events (AEs) were reported. ResultsIn all, 620 patients were randomized (pregabalin, n = 313; placebo, n = 307). Improvement in MPS with pregabalin versus placebo was not significant (P = 0.0559). Post hoc sensitivity analyses, excluding one patient/site due to Good Clinical Practice (GCP) non-compliance, showed pregabalin significantly improved MPS when excluding the patient (P = 0.0448) or site (P = 0.0142). Pregabalin significantly improved weekly MPS (P = 0.0164) and 50% responders at endpoint (P = 0.0384). Improvement in proportion of 30% responders, impression of change, pain intensity, and sleep did not differ significantly between the treatment groups. In the severe pDPN subpopulation, pregabalin significantly improved MPS versus placebo (P = 0.0040). The most commonly reported AE was dizziness (9.6% vs 3.9% with placebo). ConclusionsPregabalin did not significantly improve the primary measure of pain in the trial. Significant reductions in MPS were observed when excluding the GCP non-compliant patient/site and in the severe pDPN subpopulation. Pregabalin was well tolerated in Chinese pDPN patients.

AIMS:This subanalysis of a cross-sectional, nationwide study was undertaken to assess the relationship between healthy lifestyle behaviors and multiple cardiovascular risk factors among people with type 2 diabetes mellitus (T2DM).METHODS:Data collected from 25,454 participants, including demographics, lifestyle behaviors and cardiovascular risk profiles, were analyzed. Blood pressure control as well as blood glucose and blood lipid (3Bs) levels were measured as multi-risk factors for cardiovascular disease. Healthy lifestyle behaviors included regular exercise, nonsmoking status and no alcohol consumption. The relationship between the healthy lifestyle behavior(s) and control of 3B(s) was calculated.RESULTS:Of the 25,454 eligible participants, 4171 (16.4%) were current smokers, 2011 (7.9%) currently consumed alcohol, and 11,174 (43.9%) did not exercise. In total, 654 (2.6%) reported all three unhealthy lifestyle behaviors. Most participants (71.1%) had received at least a high school education and were more likely to smoke and drink as compared to those with lower education. Unhealthy lifestyle behaviors were commonly found in participants with low atherosclerosis risk, such as non-elderly people and those with an above-college education level. Unhealthy lifestyle is associated with poor 3B control and worse medication adherence.CONCLUSIONS:Unhealthy lifestyles are common in Chinese people with T2DM, especially in people who are non-elderly and above-college educated. Interventions aimed at changing risky lifestyle behaviors are required for improved outcomes for Chinese patients with T2DM.

Aims To examine treatment patterns following basal insulin ( BI ) introduction in type 2 diabetes mellitus ( T2DM ) patients under real‐world conditions across C hina. Materials and methods Overall, 18 995 patients inadequately controlled ( HbA1c ≥ 53 mmol/mol [7%]) with oral antihyperglycaemic drugs ( OADs ) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2) and 6 months (visit 3). Type of BI was initiated at physicians’ discretion. Results Retention with BI therapy at 6 months was 75.6%. Use of long‐acting BI predominated, with insulin glargine accounting for 71%, detemir 13% and Neutral Protamine Hagedorn ( NPH ) insulin 16%. Over 70% of long‐acting users maintained the same initial BI at visit 3, while 40% of NPH users switched treatment and 24.4% of participants initiated BI with prandial insulin. The initial mean (± SD ) dose of BI and total insulin was 0.18 ± 0.07 and 0.25 ± 0.19 IU /kg, respectively, with a mean increase of daily dose by 0.03 and 0.02 IU /kg after 6 months, respectively. Only 56.6% of insulin users reported dose titration at visit 3. Mean HbA1c was 81 mmol/mol (9.6%) at baseline and 57 mmol/mol (7.4%) at 6 months. The frequency of hypoglycaemia was 1.61 and 2.07 episodes/patient‐year at baseline and 6 months, respectively. Conclusions In real‐world clinical settings, add‐on BI therapy in T2DM patients is associated with significant improvement in glycaemic control without overtly compromising safety related to hypoglycaemia and weight gain. Evolution of insulin treatment regimens varied among patients, but dose titration was suboptimal. More active BI dose titration might further improve glycaemic outcome in patients receiving BI therapy. Video Abstract A free Video Abstract to accompany this article is available at https://vimeo.com/212655959

Objective To summarize the current status and change of anti-diabetic medication regimen of diabetic patients hospitalized to different departments in Chinese PLA General Hospital. Methods The clinical data of patients with diabetes admitted to Chinese PLA General Hospital from January 2001 to May 2014 were collected(the patients hospitalized in the Department of Endocrinology were excluded). Total of 10 041 patients were selected by stratified random sampling. The type of anti-diabetic medication regimen in different departments and the variation on antihyperglycemic treatment strategies with time were retrospectively analyzed.Data were compared with chi-square among the groups.Results A total of 10 041 patients with diabetes mellitus were selected,of whom 5 502(54.8%)were male and 4 539 (45.2%)were female.The overall mean age was(62±14)years.Of all the patients,49.8% were treated with oral antidiabetic drugs (OADs) alone, 37.2% used insulin only and 13.0% of the patients received OADs plus insulin. About 54.7% of patients in internal medicine department were treated with OADs, among which, monotherapy accounted for 36.5%, two OADs combination took up 16.5%, three or more OADs combination took up 1.7%. While those in surgical department preferred insulin for treatment when compared their counterparts in internal medicine departments[56.2%(2 526/4 497)vs 45.3%(2 510/5 544), χ2=117.928, P<0.001]. During the past 15 years, the number of patients treated with OADs alone reduced [71.1%(589/828) vs 46.0%(2 315/5 036), χ2=271.087, P<0.01], while the number of those using insulin alone or OADs plus insulin increased[22.1%(183/828)vs 38.9%(1 963/5 036),6.8%(56/828)vs 15.1%(758/5 036),χ2=120.369,96.989,both P<0.01].Conclusions The anti-diabetic medication regimen is different in different departments.Insulin therapy was more common in surgical department than in internal medicine department. In the past 15 years, the percentage of patients using insulin alone or OADs plus insulin increases with time.

Aims: To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.Methods: In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c >= 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.Results: A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% +/- 2.1%) and detemir groups (2.2% +/- 2.1%) was higher than that in the NPH group (2.0% +/- 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 +/- 2.9 kg) compared with the glargine (+0.1 +/- 3.0 kg) and NPH (+0.3 +/- 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.Conclusion: In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

The ACE trial is examining whether acarbose, an insulin-sparing postprandial glucose-lowering agent, can reduce cardiovascular (CV) events in patients who have coronary heart disease (CHD) and impaired glucose tolerance (IGT), with prevention of type 2 diabetes (T2D) as a secondary outcome.1., 2. This update report evaluates the impact of the protocol-driven 4-week CV risk management optimization strategy during the run-in period, lists participant baseline characteristics, and examines whether temporal differences occurred during the 7-year recruitment period.

BACKGROUND:Type 2 diabetes mellitus (T2DM) is a significant burden in China, where approximately 114 million patients have been diagnosed with diabetes. Chinese patients present with prominent β-cell failure, with resulting deficiency in insulin secretion, particularly early phase insulin secretion leading to postprandial hyperglycemia. Sitagliptin, a selective once-daily oral dipeptidyl peptidase-4 inhibitor, has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents, including sulfonylureas and metformin. METHODS:This was a multicenter randomized double-blind placebo-controlled study conducted in China. The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c, fasting plasma glucose (FPG) and 2-h post-meal glucose (PMG). Patients were aged 18-79 years, had T2DM with inadequate glycemic control, and were taking a sulfonylurea, with or without metformin. RESULTS:After 24 weeks, sitagliptin reduced HbA1c, FPG, and 2-h PMG significantly more than placebo (between-treatment differences: -0.61 %, -16.8 mg/dL, and -32.9 mg/dL, respectively; P < 0.001 for all). The addition of sitagliptin was generally well tolerated, with a comparable incidence of adverse events and drug-related adverse events in both treatment groups. The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group (25/248 [10.1 %] vs 13/249 [5.2 %], respectively; P = 0.042). CONCLUSIONS:Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea, with or without metformin therapy. The addition of sitagliptin was generally well tolerated. (clinicaltrials.gov: NCT01590771).

OBJECTIVE:To investigate the effect of healthcare provider (HCP) type (primary vs. specialist) on glycaemic control and other treatment parameters. RESEARCH DESIGN AND METHODS:Study of Once-Daily Levemir (SOLVE(™) ) is an international, 24-week, observational study of insulin initiation in people with type 2 diabetes. RESULTS:A total of 17,374 subjects were included, comprising 4144 (23.9%) primary care subjects. Glycaemic control improved in both HCP groups from baseline to final visit [glycated haemoglobin (HbA1c) -1.2 ± 1.4% (-13.1 ± 15.3 mmol/mol) and -1.3 ± 1.6% (-14.2 ± 17.5 mmol/mol), respectively]. After adjustment for known confounders, there was no statistically significant effect of HCP group on final HbA1c [-0.04%, 95% confidence interval (CI) -0.09 to -0.01 (-0.4 mmol/mol, 95% CI -1.0-0.1 mmol/mol), p = 0.1590]. However, insulin doses at the final visit were higher in primary care patients (+0.06, 95% CI 0.06-0.07 U/kg, p < 0.0001). Logistic regression demonstrated a significant effect of HCP type (primary vs. specialist care) on hypoglycaemia risk [odds ratio (OR) 0.75, 95% CI 0.64-0.87, p = 0.0002]. Primary care physicians took more time to train patients and had more frequent contact with patients than specialists (both p < 0.0001). CONCLUSIONS:Primary care physicians and specialists achieved comparable improvements in glycaemic control following insulin initiation.

Background The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China.Methods We did a cross-sectional survey using data from the China National HbA(1c) Surveillance System (CNHSS), including 222 773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis.Findings Of 222 773 patients recruited from April 1, 2012, to June 30, 2012, 24 316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11.1% vs 4.9%; p<0.0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1.91, 95% CI 1.81-2.02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1.13, 1.06-1.20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes.Interpretation Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes.