Diabetic Retinopathy in 2011: Further Insights From New Epidemiological Studies and Clinical Trials

10.2337/dc11-0225Diabetes Care3441066-1067DICA

A Summary of the ADVANCE Trial

The publication of the U.K. Prospective Diabetes Study (UKPDS) in 1998 helped to shape the management of type 2 diabetes in recent years (1). The study demonstrated several points. First, sulfonylureas are as safe as insulin in controlling blood glucose. Second, metformin reduced cardiovascular disease in an overweight subgroup. Third, the same benefit of glycemic control in reducing microvascular disease (previously noted in type 1 diabetes) is applied equally to patients with type 2 diabetes. A separation in A1C of ∼1% in the UKPDS reduced the risk of microvascular disease (largely diabetic retinopathy) by ∼25%. This reflected the data from the Diabetes Control and Complications Trial, where a separation in A1C of 2% in intensive and standard groups led to a reduction in microvascular disease of ∼50% (2). A fourth demonstration was that there was no significant reduction in macrovascular disease but a trend toward fewer myocardial infarctions with more intensive glucose control. Fifth, using the current treatment of the time (first-generation sulfonylureas, human ultratard insulin, or metformin), it proved impossible to maintain glucose control, which tended to deteriorate throughout the study. It is now generally believed that the progressive fall in endogenous insulin production as β-cell numbers decline makes it difficult, if not impossible, to maintain tight control using standard treatment. Sixth, the UKPDS also showed that in those patients with hypertension, lowering blood pressure (BP) to moderate levels with either captopril or atenolol could reduce microvascular disease (3). In a subsequent study, the UKPDS investigators presented the rates of both micro- and macrovascular disease according to the achieved levels of A1C during the study (4). They showed a linear relationship between A1C and both groups of complications. The implication of the article was that if glycemic control could be tightened below the levels achieved in the UKPDS, then it might be possible to reduce rates, not only of microvascular complications, but also cardiovascular disease as well. The aim of the glucose arm of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (5) was to build on the information gained by the UKPDS and to answer the question as to whether intensifying glucose control to achieve an A1C of <6.5% would provide additional benefit in reducing the risk of both micro- and macrovascular disease. ADVANCE also asked questions about BP lowering in patients with type 2 diabetes. The aims of the BP arm were to establish whether routine provision of BP-lowering therapy produced additional benefits in terms of macro- and microvascular disease, irrespective of baseline BP, and added to the benefits produced by other cardiovascular preventive therapies, including ACE inhibitors

Demographics, insulin use and clinical targets in type 2 diabetes insulin users: comparison of a local integrated diabetes service vs a UK-wide cohort

Insulin-treated patients with type 2 diabetes require specialist multidisciplinary input to achieve treatment targets. We compared the demographics, achievement of combined NICE targets for HbA1c (≤7.5%), blood pressure (<140/80mmHg) and total cholesterol (<4mmol/L), and insulin use between patients from a local integrated diabetes service with those from a representative UK population. A cross-sectional evaluation of individual patient data from six randomly-selected primary care practices in Erewash (Integrated) Diabetes Service was compared with The Health Improvement Network (THIN) UK primary care database. Baseline age (61.5 years vs 65.8 years; p < 0.0001) and duration of insulin use (4.3 vs 6.3 years; p < 0.0001) use were lower in the THIN cohort. Mean HbA1c was similar between the two cohorts but weight, blood pressure, total and LDL cholesterol were significantly lower in the Erewash population compared with THIN. The combined achievement of HbA1c, total cholesterol and blood pressure was 17.5% in the Erewash cohort compared with 9.6% in the THIN cohort (p < 0.0001). There was a higher proportion of insulin users on basal-bolus than on premix in the Erewash cohort (89.3% vs 10.7%) compared with THIN (59.0% vs 41.1%). The proportion of patients who received concurrent oral glucose-lowering therapies in the Erewash integrated service was lower, except for SGLT2 inhibitors (2.5% in the Erewash cohort vs 0.5% in THIN; p < 0.0001). This model of an integrated diabetes service appears to confer better achievement for the NICE defined clinical targets compared with the THIN cohort. Further studies are required to investigate the impact of this service model on health economics, patient pathway and patient experience. Copyright © 2017 John Wiley & Sons

The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c &lt;7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

Triple Combination Therapy Using Metformin, Thiazolidinedione, and a GLP-1 Analog or DPP-IV Inhibitor in Patients with Type 2 Diabetes Mellitus

Although there is no HbA1c threshold for cardiovascular risk, the American Diabetic Association-recommended goal of HbA1c < 7.0% appears to be unacceptably high. To achieve an optimal HbA1c level goal of 6.0% or less, a high dosage of sulfonylureas and insulin would be required; the trade-off would be the common adverse effects of hypoglycemia and weight gain. In contrast, hypoglycemia is uncommon with insulin sensitizers and GLP-1 analogs, allowing the physician to titrate these drugs to maximum dosage to reduce HbA1c levels below 6.0% and they have been shown to preserve β-cell function. Lastly, weight gain is common with sulfonylurea and insulin therapy, whereas GLP-1 analogs induce weight loss and offset the weight gain associated with TZDs. A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which has antiatherogenic effects and improves hepatic insulin sensitivity), a TZD (which improves insulin sensitivity and preserves β-cell function with proven durability), and a GLP-1 analog (which improves β, α-cell function and promotes weight loss) or a dipeptidyl peptidase IV inhibitor in patients with type 2 diabetes mellitus

Stepwise screening for diabetes identifies people with high but modifiable coronary heart disease risk. The ADDITION study

AIMS/HYPOTHESIS: The Anglo-Danish-Dutch study of intensive treatment in people with screen-detected diabetes in primary care (ADDITION) is a pragmatic randomised controlled trial of the effectiveness of intensified multi-factorial treatment on 5 year cardiovascular morbidity and mortality rates in people with screen-detected type 2 diabetes in the Netherlands, UK and Denmark. This paper describes the baseline characteristics of the study population, their estimated risk of coronary heart disease and the extent to which that risk is potentially modifiable. METHODS: Stepwise screening strategies were performed using risk questionnaires and routine general practice data plus random blood glucose, HbA(1c) and fasting blood glucose measurement. Diabetes was diagnosed using the 1999 World Health Organization criteria and estimated 10 year coronary heart disease risk was calculated using the UK Prospective Diabetes Study risk engine. RESULTS: Between April 2001 and December 2006, 3,057 people with screen-detected diabetes were recruited to the study (mean age 59.7 years, 58% men) after a stepwise screening programme involving 76,308 people screened in 334 general practices in three countries. Their median estimated 10 year risk of coronary heart disease was 11% in women (interquartile range 7-16%) and 21% (15-30%) in men. There were differences in the distribution of risk factors by country, linked to differences in approaches to screening and the extent to which risk factors had already been detected and treated. The mean HbA(1c) at recruitment was 7.0% (SD 1.6%). Of the people recruited, 73% had a blood pressure >/=140/90 and of these 58% were not on antihypertensive medication. Cholesterol levels were above 5.0 mmol/l in 70% of participants, 91% of whom were not being treated with lipid-lowering drugs. CONCLUSIONS/INTERPRETATION: People with type 2 diabetes detected by screening and included in the ADDITION study have a raised and potentially modifiable risk of CHD. ClinicalTrials.gov ID no.: NCT 00237549

Barriers to following dietary recommendations in Type 2 diabetes

Aims  To evaluate barriers to following dietary recommendations in patients with Type 2 diabetes. Methods  We conducted focus groups and surveys in urban and suburban VA and academic medical centres. For the written survey, a self-administered questionnaire was mailed to a random sample of 446 patients with diabetes. For the focus groups, six groups of patients with diabetes (three urban, three suburban) were conducted, with 6–12 participants in each group. The focus groups explored barriers across various types of diabetes self-management; we extracted all comments relevant to barriers that limited patients’ ability to follow a recommended diet. Results  The written survey measured the burden of diabetes therapies (on a seven-point rating scale). Moderate diet was seen as a greater burden than oral agents (median 1 vs. 0, P  = 0.001), but less of a burden than insulin (median 1 vs. 4, P  < 0.001). A strict diet aimed at weight loss was rated as being similarly burdensome to insulin (median 4 vs. 4, P  = NS). Despite this, self-reported adherence was much higher for both pills and insulin than it was for a moderate diet. In the focus groups, the most commonly identified barrier was the cost (14/14 reviews), followed by small portion sizes (13/14 reviews), support and family issues (13/14 reviews), and quality of life and lifestyle issues (12/14 reviews). Patients in the urban site, who were predominantly African-American, noted greater difficulties communicating with their provider about diet and social circumstances, and also that the rigid schedule of a diabetes diet was problematic. Conclusions  Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients’ ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients’ preferences and barriers when setting goals for treatment. Diabet. Med. (2004)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73213/1/j.1464-5491.2004.01342.x.pd