Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit.

AIMS: We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes population. METHODS: The U.K. National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. RESULTS: The cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. CONCLUSIONS: The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS: A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients. METHODS: For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n = 15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients. RESULTS: Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n = 10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results. CONCLUSIONS/INTERPRETATION: Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Identifying additional patients with diabetic nephropathy using the UK primary care initiative.

AIMS: The aim of this study was to use general practice data to estimate the prevalence of diabetic nephropathy within the registered diabetes patients and examine variation in practice prevalence and management performance since introduction of this initiative. METHODS: Reported quality indicators from the Northern Ireland General Practice Quality and Outcomes Framework were analysed for diabetes and diabetic nephropathy prevalence and management in the period 2004-2008. Variation in prevalence at practice level was assessed using multiple linear regression adjusting for age, practice size, deprivation and glycaemic control. RESULTS: In 2006-2007, 57,454 (4.1%) adult diabetic patients were registered in the denominator population of 1.4 million compared with 51,923 (3.8%) in 2004-2005 (mean practice range 0.5-7.7%). Diabetic nephropathy prevalence was 15.1 and 11.5%, respectively (8688 and 5955 patients). Documented diabetic nephropathy prevalence showed marked variation across practices (range 0-100%) and was significantly negatively correlated with diabetes list size, albumin creatinine ratio testing rates and renin-angiotensin-aldosterone system blockade use and positively correlated with exception reporting rates. Specifically, for every increase in 100 diabetic patients to a register, documented diabetic nephropathy prevalence reduced by 40% (P=0.003). On the positive side, median albumin-creatinine ratio testing rates doubled to 82% compared with figures in the pre-Framework era. CONCLUSIONS: Implementation of the Northern Ireland General Practice Quality and Outcomes Framework has positively benefitted testing for diabetic nephropathy and increased numbers of detected patients in a short space of time. Large variation in diabetic nephropathy prevalence remains and is associated with diabetes registry size, screening and treatment practices, suggesting that understanding this variation may help detect and better manage diabetic nephropathy.

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

AIMS/HYPOTHESIS: Glomerular hyperfiltration is a well-established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR. METHODS: A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement of GFR and presence or absence of hyperfiltration. RESULTS: We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20-6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p = 0.05, measure of degree of inconsistency = 48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min(-1) 1.73 m(-2) (95% CI 5.0-22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p < 0.01). CONCLUSIONS/INTERPRETATION: In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

Influence of prolonged hospitalization on overall bed occupancy: a five-year single-centre study.

BACKGROUND: Effective bed use is crucial to an efficient NHS. Current targets suggest a decrease in mean occupancy as the most appropriate method of improving overall efficiency. The elderly and those suffering from complex medical problems are thought to account for a high proportion of overall bed occupancy. AIM: To assess the effect of prolonged hospital stay (>100 days) on overall bed occupancy in a modern teaching hospital. DESIGN: Retrospective analysis. METHODS: Analysis of all admission episodes (n = 117,178) over a five-year period in a large teaching hospital in a single UK region, serving a population of approximately 200,000. A logistic regression multi-factorial model was used to assess the effect of demographic and diagnostic variables on duration of stay. RESULTS: A prolonged stay (>100 days) was seen in 648 admission episodes (0.6%). These accounted for 11% of the overall bed occupancy over the 5-year period. Excluding all prolonged admission episodes from our analysis made no difference to the overall median length of stay. DISCUSSION: Prolonged hospitalizations have a significant impact on bed occupancy. Targeting these very long (>100 days) hospital stays may better improve overall efficiency, compared to targeting mean or median length of stay.

Regulation by P2 agonists of the intracellular calcium concentration in epithelial cells freshly isolated from rat trachea.

Epithelial cells were isolated from rat trachea by incubation of the organ in a calcium-free medium. The intracellular concentration of calcium ([Ca(2+)](i)) was measured with the calcium-sensitive fluorescent dye fura2. In resting conditions, the cells maintained a low [Ca(2+)](i) in spite of the presence of millimolar concentration of calcium in the incubation medium. These cells had retained intracellular stores of calcium which were emptied after exposure of the cells to thapsigargin, an inhibitor of intracellular calcium ATPases. Substance P (125 nM) transiently increased 2.5-fold the [Ca(2+)](i). ATP (1 mM) doubled the [Ca(2+)](i) after a few seconds and further induced a sustained increase of the [Ca(2+)](i). Coomassie blue fully blocked the response to ATP and extracellular magnesium only inhibited the delayed response to ATP. Among purinergic analogs, only benzoyl-ATP (Bz-ATP), an agonist on P2X ionotropic purinergic receptors, reproduced the response to ATP. UTP and 2-methylthioATP (two agonists on P2Y metabotropic purinergic receptors) transiently increased the [Ca(2+)](i). Thapsigargin, ATP and Bz-ATP increased the uptake of extracellular calcium. RT-PCR analysis revealed that two metabotropic receptors (P2Y(1) and P2Y(2)) and two ionotropic receptors (P2X(4) and P2X(7)) were expressed by the cells present in the suspension. It is concluded that purinergic agonists can modulate the response of rat tracheal epithelial cells by several mechanisms. The activation of metabotropic receptors should mobilize intracellular IP(3)-sensitive calcium pools. The activation of the ionotropic receptors should not only open a non-specific cation channel leading to the entry of calcium but should also induce the formation of pores in cells expressing the P2X(7) receptors, which could be deleterious to these cells.

Segregation analysis of urinary albumin excretion in families with type 2 diabetes.

Elevated urinary albumin excretion (UAE) is a predictor of the development of nephropathy and cardiovascular mortality. To study whether genetic factors may determine UAE, we examined familial aggregation of UAE in 96 large multigenerational pedigrees ascertained for type 2 diabetes. A total of 1,269 subjects had UAE measured as the urinary albumin-to-creatinine ratio (ACR). This included 630 subjects with type 2 diabetes and 639 subjects without diabetes. A significant correlation (Spearman's correlation 0.34, P < 0.001) was found between the median ACR values determined separately in nondiabetic and diabetic members of the same family. To determine whether this familial aggregation of ACR could be explained by the transmission of 1 or more major genes and thus be suitable for gene mapping studies, segregation analyses were performed. In these analyses, ACR was modeled as a continuous trait with the inclusion of age, sex, and duration of diabetes as covariates. Likelihood ratio tests were performed to test competing hypotheses, and Akaike's information criterion was used to determine the most parsimonious models. The Mendelian model with multifactorial inheritance was supported more strongly than Mendelian inheritance alone. These analyses suggested that the best model for ACR levels was multifactorial with evidence for a common major gene. When the analyses were repeated for diabetic subjects only, the evidence for Mendelian inheritance was improved, although a single major locus with additional multifactorial effects was more strongly supported. The results from the current study suggest that levels of UAE are determined by a mixture of genes with large and small effects as well as other measured covariates, such as diabetes.

A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM.

Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04-7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.

HDL composition and HDL antioxidant capacity in patients on regular haemodialysis.

Recent evidence suggests that HDL can directly inhibit LDL oxidation, a key early stage in atherogenesis. Patients with chronic renal failure are at increased cardiovascular risk, have reduced HDL levels and altered HDL composition. We have therefore investigated whether compositional changes in HDL lead to decreased HDL antioxidant capacity in these patients. In comparison to control subject HDL, patient HDL contained less total cholesterol, cholesterol esters, phospholipids and alpha-tocopherol. LDL, HDL and LDL + HDL were standardised for protein and oxidised in the presence of Cu2+. The rate of propagation during HDL oxidation was reduced in the patient group (3.28+/-0.65 x 10(-5) vs. 4.60+/-0.97 x 10(-5) abs. U/min, P < 0.01). Lipid peroxide generation in patient HDL was decreased: 6.56+4.4 versus 13.42+/-7.0 nmol malondialdehyde (MDA)/mg HDL protein after 90 min and 14.45+/-3.8 versus 20.11+/-7.8 nmol MDA/mg HDL protein after 180 min. This is attributable to reduced HDL polyunsaturated fatty acid content in patients (0.53+/-0.12 vs. 0.72+/-0.16 mmol/g HDL, P < 0.01). The inhibitory effect of HDL on LDL oxidation was similar: 71 and 33% for patient HDL compared to 68 and 31% for control HDL, after 90 and 180 min, respectively. Compositional changes of HDL in patients on haemodialysis did not affect the antioxidant capacity of HDL after standardisation for HDL protein. However, reduced HDL levels in vivo may result in reduced HDL antioxidant capacity in these patients.

KA1-like kainate receptor subunit immunoreactivity in neurons and glia using a novel anti-peptide antibody.

Functional kainate receptors can be formed by various combinations of subunits with low (GluR5, GluR6 and GluR7) or high affinity (KA1 and KA2) for kainate. The precise contribution of each subunit to native receptors, as well as their distribution within the central nervous system (CNS) is still unclear. Here, we describe the presence of KA1-like immunoreactivity in both neurons and glial cells of the CNS, using a newly developed antiserum to a specific carboxy terminus epitope of the KA1 subunit. Intense immunoreactivity was observed in the CA3 area of the rat hippocampus. Electron microscopy revealed that immunostaining was present in dendritic structures postsynaptic to commissural-associational fibers, rather than in those contacted by mossy fiber terminals. We also observed immunostaining of CA1 pyramidal cell apical dendrites. In the cerebral cortex, KA1-like immunostaining was observed in many pyramidal neuron somata, mainly in layer V, and along their apical dendrites. A subset of gamma-amino-butyric acidic cells were also intensely stained. In the cerebellum, the antiserum selectively stained Purkinje cell somata and their dendrites as well as Bergmann glial processes. Other types of macroglia were also labeled by the KA1 antiserum. Thus, optic nerve oligodendrocytes both in vitro and in situ and cultured astrocytes were densely stained. Our results indicate that KA1-type subunits are more widely distributed throughout the CNS than previously thought. This newly developed antiserum may help to clarify the properties of kainate receptors containing KA1 or KA1-type subunits within the normal and pathological brain.

Homocysteine and B-group vitamins in renal transplant patients.

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.

Hypertension and nephropathy in diabetes mellitus: what is inherited and what is acquired?

Prolonged duration of diabetes mellitus, poor long term glycemic control and raised blood pressure have all been clearly related to the development of diabetic nephropathy. Evidence exists to suggest that a subset of individuals with diabetes have a genetic predisposition to diabetic nephropathy. Cases of diabetic nephropathy cluster in families and a parental history of hypertension is more common in patients with diabetic nephropathy. Current evidence suggests an important role for hypertension in the genetic susceptibility to diabetic nephropathy but the extent of this is unknown. While cellular and animal studies have generated a plethora of data regarding mechanisms involved in the role of hypertension and diabetic nephropathy, these are not helpful for drawing conclusions in humans. In the following review, we examine the available clinical, epidemiologic and family studies to assess the relationship between the development of hypertension and diabetic nephropathy in IDDM and NIDDM. We will demonstrate the differences in the epidemiology of hypertension in diabetes depending on the type of diabetes and thus, move the emphasis of nephropathy susceptibility away from hypertension per se. We hope to emphasize instead the homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a common genetic susceptibility exists for all types of diabetes and is conditional on cumulative exposure to hyperglycemia. Regarding the interaction of hypertension and nephropathy in diabetes mellitus, any conclusions at this time about what is inherited and what is acquired must be regarded as speculative. However we will discuss some potential mechanisms of hypertension in the evolution of nephropathy and we will allude to the role for novel genetic studies in the search for nephropathy susceptibility gene(s).

Intraoperative bupivacaine diminishes pain after lumbar discectomy. A randomised double-blind study.

A randomised double-blind study was carried out on 60 patients undergoing elective lumbar discectomy. Patients in the study group (n = 30) received an injection of 10 ml of 0.5% bupivacaine into the wound; the control group (n = 30) received none. Postoperative pain was measured by a visual analogue pain scale and by the amount of morphine administered by a patient-controlled analgesia system. Patients in the study group had lower pain scores, used less morphine, waited longer until their first demand for analgesia and reported their postoperative pain to be less severe.

Experimental effects on surrounding fibrous capsule formation from placing steroid in a silicone bag-gel prosthesis before implantation.

Soft-gel miniprostheses of silicone were implanted subcutaneously into 75 male rats. Groups of prostheses were preinjected with saline, a commercial form of triamcinolone acetonide, or a suspension of crystalline triamcinolone acetonide. The softness of the prosthesis mound later was measured objectively, and the capsules surrounding the implants were analyzed by histology, SEM, and chemistry, at various intervals up to 120 days after implantation. The control implants developed a normal laminar capsule. With an incidence increasing up to 100 percent at 120 days, the steroid-treated implants were surrounded by capsules lacking an inner membrane. The inner membrane of the laminar capsule had a high protein content (relative to normal tissue) and a relatively reduced collagen content, while the diffuse capsule resulting from the TA treatment had a high protein content and a high collagen content (about the same as normal tissue). No differences were found in the softness of the mounds of the implanted prostheses. The effect of the TA treatment was explained on the basis of its collagenolytic effect, which could gradually erode the normal capsule membrane. Capsule firmness could not be related to the architecture or the protein or collagen content in our findings. We hypothesize that normal capsule firmness may be related to the amount and kind of interconnection between the loose outer zone of connective tissue and the surrounding tissue.

Experimental study of tissue response to ruptured gel-filled mammary prostheses.

Miniature "soft gel" filled breast prostheses were implanted into rats, and half of these were purposefully ruptured upon insertion. At sacrifice of the animals later, the position of the exuded gel, the variability of the capsule thickness, and the extent of the capsule formation were evaluated. The capsule thickness was significantly increased around the ruptured prostheses, in response to the exuded gel. Also, the gel migrated through the fibrous capsule and into the surrounding tissue, eliciting an inflammatory response there to produce capsule thickening.

On how altered glutamate homeostasis may contribute to demyelinating diseases of the CNS.

Glial cells communicate reciprocally with neurons in multiple ways, both in synaptic and non-synaptic regions of the central nervous system. In the latter, neuron to glial and glial to glial signals can be mediated by neurotransmitters. Here, we review the presence and some of the functional properties of glutamate transporters and receptors in oligodendrocytes. In addition, we present data illustrating that alterations in glutamate homeostasis can be excitotoxic to oligodendroglia and that the tissue lesions caused by overactivation of glutamate receptors resemble those observed in demyelinating diseases such as multiple sclerosis. Overall, this information indicates that aberrant glutamate signaling may contribute to the development of some white matter pathologies.

The effect of column age on system suitability parameters for an HPLC assay of bitolterol mesylate aerosols.

A reversed-phase ion-pairing HPLC method is developed for bitolterol mesylate (Tornalate, Winthrop-Breon) in aerosol dosage forms. Using data acquired by this method during a two-year period, the effect of ODS-3 column age on system suitability parameters is assessed. A BASIC program is used to calculate the resolution factor between bitolterol and colterol triester, capacity factors, number of theoretical plates, and tailing factors in studies that followed the performance of one column during this time period and five columns of different ages under normal usage. A 15 to 30% reduction in column performance per year is found.

Postoperative analgesia following total hip replacement: a comparison of intrathecal morphine and diamorphine.

Sixty patients undergoing elective total hip replacement under spinal anaesthesia were randomly assigned to receive either intrathecal (IT) diamorphine 0.75 mg (n = 30) or IT morphine 1.0 mg (n = 30). Postoperative pain scores, analgesic requirements and side effects were assessed by a blinded observer. Postoperative pain scores were broadly similar and satisfactory for both groups but the amount of additional IV morphine required to achieve this was significantly reduced in the morphine compared with the diamorphine group (P < 0.05). Twelve of the morphine group required no postoperative analgesics compared with four in the diamorphine group (P < 0.02). There were no differences between the groups in the incidence of side effects such as emesis and pruritus. No significant postoperative respiratory depression was noted. In the doses used intrathecal morphine provided superior postoperative analgesia to that of intrathecal diamorphine.

Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit.

BACKGROUND: Obesity is increasingly prevalent in many countries. Obesity is a major risk factor for the development of type 2 diabetes but its relationship with diabetic kidney disease (DKD) remains unclear. Some studies have suggested that the metabolic syndrome (including obesity) may be associated with DKD in type 1 diabetes. AIM: To investigate the association between obesity and DKD. DESIGN: Retrospective cross-sectional study. METHODS: National Diabetes Audit data were available for the 2007-08 cycle. Type 1 and 2 diabetes patients with both a valid serum creatinine and urinary albumin:creatinine ratio were included. DKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), albuminuria or both. Logistic regression was used to analyse associations of obesity (body mass index ≥30 kg/m(2)) and other variables including year of birth, year of diagnosis, ethnicity and stage of kidney disease. RESULTS: A total of 58 791 type 1 and 733 769 type 2 diabetes patients were included in the analysis. After adjustment, when compared with type 1 diabetes patients with normal renal function those with DKD were up to twice as likely to be obese. Type 2 DKD patients were also more likely to be obese. For example, type 2 diabetes patients with an eGFR <15 ml/min/1.73 m(2) and normoalbuminuria, microalbuminuria or macroalbuminuria were all more likely to be obese; odds ratios (95% CI) 1.65 (1.3-2.1), 1.56 (1.28-1.92) and 1.27 (1.05-1.54), respectively. CONCLUSION: This study has highlighted a strong association between obesity and kidney disease in type 1 diabetes and confirmed their association in type 2 diabetes.