Rudy Bilous

Diabetes prevalence and socioeconomic status: a population based study showing increased prevalence of type 2 diabetes mellitus in deprived areas

OBJECTIVE To establish the relation between socioeconomic status and the age-sex specific prevalence of type 1 and type 2 diabetes mellitus. The hypothesis was that prevalence of type 2 diabetes would be inversely related to socioeconomic status but there would be no association with the prevalence of type 1 diabetes and socioeconomic status. SETTING Middlesbrough and East Cleveland, United Kingdom, district population 287 157. PATIENTS 4313 persons with diabetes identified from primary care and hospital records. RESULTS The overall age adjusted prevalence was 15.60 per 1000 population. There was a significant trend between the prevalence of type 2 diabetes and quintile of deprivation score in men and women (χ2 for linear trend, p<0.001). In men the prevalence in the least deprived quintile was 13.4 per 1000 (95% confidence intervals (95% CI) 11.44, 15.36) compared with 17.22 per 1000 (95% CI 15.51, 18.92) in the most deprived. For women the prevalence was 10.84 per 1000 (95% CI 9.00, 12.69) compared with 15.48 per 1000 (95% CI 13.84, 17.11) in the most deprived. The increased prevalence of diabetes in the most deprived areas was accounted for by increased prevalence of type 2 diabetes in the age band 40–69 years. There was no association between the prevalence of type 1 diabetes and socioeconomic status. CONCLUSION These data confirm an inverse association between socioeconomic status and the prevalence of type 2 diabetes in the middle years of life. This finding suggests that exposure to factors that are implicated in the causation of diabetes is more common in deprived areas.

Microvascular disease: what does the UKPDS tell us about diabetic nephropathy?

The UK Prospective Diabetes Study is the largest study in Type 2 diabetes with pre‐specified renal outcomes. The study showed that the natural history of nephropathy in newly diagnosed Type 2 diabetic patients was similar to that described previously in those with Type 1 diabetes. Around 2% per annum progress from normo‐ to micro‐albuminuria [urinary albumin concentration (UAC) > 50 mg/l] and a further 2% from microalbuminuria to clinical grade proteinuria (UAC > 300 mg/l). Mortality rates for those with nephropathy are high, increasing from 1.4% per annum (normoalbuminuria) to 4.6% per annum (clinical grade proteinuria), and to 19.2% per annum for those with renal impairment.

Resolution of lipohypertrophy following change of short-acting insulin to insulin lispro (Humalog®)

Lipohypertrophy as a local complication of insulin therapy is well recognized. Despite improvements in insulin purity and the introduction of recombinant human insulin its prevalence has remained high. Rotation of injection sites can reduce the frequency of the problem but does not abolish it. The importance of this complication is not only cosmetic but also in its impact on insulin absorption, and hence glycaemic control. We report a patient who had intractable lipohypertrophy with human recombinant insulin but experienced no such problem when converted onto the insulin analogue lispro. We suggest that the faster speed of absorption of insulin lispro may lead to less hypertrophic stimulation of subcutaneous adipocytes. This difference may be clinically useful in susceptible individuals. Copyright

Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril

Aims The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus.

St Vincent Declaration, 1994: Guidelines for the Prevention of Diabetic Renal Failure

Diabetic nephropathy is a major cause of premature death in diabetic patients, largely from uraemia and cardiovascular disease. Diabetic nephropathy develops in about 30% of people with insulin-dependent diabetes mellitus. The cumulative risk of nephropathy in people with non-insulin-dependent diabetes varies considerably with ethnic origin. It ranges from 25 % in individuals of European origin to around 50% in other ethnic groups such as the Afro-Caribbean, Asian Indians, and the Japanese. In the UK geographic areas at high density of these ethnic groups are likely to experience a higher incidence of renal disease. Asian Indians develop non-insulin-dependent diabetes more frequently and at a younger age than Europeans and Afro-Caribbean have a significantly higher frequency of arterial hypertension. All these factors are believed to contribute to their higher risk of kidney failure. Overall non-insulin-dependent diabetes is significantly more common than insulin-dependent diabetes and the number of non-insulin-dependent diabetic patients being accepted into renal replacement therapy (RRT) programmes is now equal, if not greater, than that of insulin-dependent diabetics. In Europe diabetes is the only increasing cause of end-stage renal failure and diabetic patients represent around 13 % of all patients receiving RRT. This percentage rises to approximately 30% in the United States of America. The cost of renal replacement therapy for end-stage diabetic renal failure in the United States was around

Irbesartan delays progression of nephropathy as measured by estimated glomerular filtration rate: post hoc analysis of the Irbesartan Diabetic Nephropathy Trial

2 thousand million in 1991.

Risk and recurrence of serious adverse outcomes in the first and second pregnancies of women with preexisting diabetes.

BACKGROUND The Irbesartan Diabetic Nephropathy Trial (IDNT) demonstrated that irbesartan significantly slowed established Type 2 diabetic nephropathy progression. Estimated glomerular filtration rate (eGFR), now widely used to monitor chronic kidney disease (CKD) progression, was not previously examined in IDNT. This post hoc analysis aimed to confirm IDNT results using eGFR as principal outcome measure. METHODS Mean change in eGFR from baseline (ΔeGFR) was analysed using linear mixed-effects models over time and analysis of covariance at end of study on an intention-to-treat basis. Potential treatment response moderators and/or mediators assessed were CKD stage, blood pressure (BP) and proteinuria. RESULTS Irbesartan significantly slowed the rate of ΔeGFR decline from 6 to 21 months (P = 0.0048) and 24 to 48 months (P < 0.0001) versus amlodipine and placebo, despite a faster decline in the first month. The longer patients remained on irbesartan the greater the benefit (model-derived estimates for 6-21 and 24-48 month periods were -0.3354 and -0.1947 mL/min/1.73 m(2)/month, respectively). Irbesartan slowed the rate of ΔeGFR decline irrespective of baseline CKD stage, BP or proteinuria level. Irbesartan produced rapid and sustained proteinuria reductions, which only partially mediated treatment response. Irbesartan increased serum potassium, but levels stabilized from 6 to 48 months. CONCLUSIONS In patients with established Type 2 diabetic nephropathy and CKD Stages 1-5, irbesartan safely and significantly slowed the rate of ΔeGFR decline (-2.34 mL/min/1.73 m(2)/year) compared to amlodipine (-3.76 mL/min/1.73 m(2)/year) and placebo (-3.52 mL/min/1.73 m(2)/year). This rate of decline was slower with longer duration of irbesartan treatment and only partly explained by observed reductions in BP and proteinuria.

Universal screening to identify gestational diabetes: A multi-centre study in the North of England

OBJECTIVE Women with preexisting (type 1 or type 2) diabetes experience an increased risk of serious adverse pregnancy outcomes. It is not known, however, how these risks change between the first and second pregnancy and whether there is an increased risk of recurrence. This study describes the absolute risks and recurrence of serious adverse pregnancy outcomes in 220 women with preexisting diabetes. RESEARCH DESIGN AND METHODS A total of 440 pregnancies occurring in 220 women with preexisting diabetes who delivered successive singleton pregnancies in the North of England during 1996–2008 were identified from the Northern Diabetes in Pregnancy Survey (NorDIP). Predictors of serious adverse outcome were estimated by competing-risks regression. RESULTS Sixty-seven first pregnancies (30.5%) ended in serious adverse outcome, including 14 (6.4%) with congenital anomalies and 53 (24.1%) additional fetal or infant deaths. Thirty-seven second pregnancies (16.8%) ended in serious adverse outcome—half the rate among first pregnancies (P = 0.0004)—including 21 (9.5%) with congenital anomalies and 16 (7.3%) additional fetal or infant deaths. Serious adverse outcomes in the second pregnancy occurred twice as frequently in women who experienced a previous adverse outcome than in those who did not (26.9% vs. 12.4%, P = 0.004), but previous adverse outcome was not associated with preparation for the following pregnancy. CONCLUSIONS Serious adverse outcomes are less common in the second pregnancies of women with preexisting diabetes, although the risk is comparable in those whose first pregnancy ends in adverse outcome. Reducing the risk of recurrence may require more support in the immediate period after an adverse pregnancy outcome.

Should women with diabetic nephropathy considering pregnancy continue ACE inhibitor or angiotensin II receptor blocker therapy until pregnancy is confirmed? Reply to Lewis G and Maxwell AP [letter]

We conducted an audit of treatment and outcomes in 116 women with gestational diabetes. These women received intense monitoring and high levels of medical and obstetric intervention. 24% would not have been identified by risk factor based screening. Cost effective strategies to identify all women with gestational diabetes are needed.

Improving prognosis in NIDDM patients

To the Editor: We were pleased to read the letter by Lewis and Maxwell [1], which highlights the need for extra vigilance when caring for and counselling women with diabetes with a history of microvascular disease. Our own observational research shows that, in addition to the consequence of typically poor glycaemic control, women with pre-pregnancy retinopathy or nephropathy experience additional increases in their risks of perinatal death and congenital anomaly [2, 3]. For this reason, we have suggested that all women with diabetes and a history of retinopathy or nephropathy receive additional support when planning their pregnancy [3]. In their letter, Lewis and Maxwell recommend a more specific pharmacological solution by proposing that ‘women with diabetic nephropathy who are considering pregnancy should, after appropriate counselling, be encouraged to consider continuing their ACEI [ACE inhibitor] or ARB [angiotensin II receptor blocker] therapy up until the first positive pregnancy test in the first trimester’ [1]. Although we agree with the need to minimise the risk of serious maternal complications, such as pre-eclampsia, we are less persuaded by Lewis and Maxwell’s assertion that administering ACEI and ARB medication before pregnancy and until pregnancy is confirmed, ‘offers the best chance of safe delivery of a healthy child for these women’ [1]. As the authors discuss, the fetal consequences of ACEI and ARB therapy use in pregnancy remain unclear. While it is well established that these drugs cause fetal and neonatal complications when used during the second and third trimesters of pregnancy [4], the impact during the first-trimester—the most sensitive period for severe teratogenicity—is unclear. The work by Cooper et al [5] remains the only epidemiological study to demonstrate an increased risk associated with ACEI and ARB use compared with other anti-hypertensive medications specifically. However, with the exception of Li et al [6], all studies that have performed similar investigations—i.e, comparing first-trimester exposure between groups of women with hypertension—have had modest sample sizes. Even the meta-analysis by Walfisch et al was hindered by imprecision [7]. Although the conclusion seems unambiguous (that exposure ACEIs and ARBs during the first trimester is not associated with an elevated risk of major malformations compared with other antihypertensive medications), the uncertainty around the point estimate, itself not insignificant (RR 1.41, 95% CI 0.66, 3.04), is insufficient to exclude a medium-to-large teratogenic effect [7]. Of more concern, however, are the frequent methodological issues. Li et al [6], P. W. G. Tennant (*) : S. V. Glinianaia : J. Rankin : R. Bell Institute of Health & Society, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne NE2 4AX, UK e-mail: peter.tennant@ncl.ac.uk