Triglyceride-glucose index: A surrogate marker of homeostasis model assessment of insulin resistance to predict diabetic nephropathy.

Objectives: To determine the association of triglyceride-glucose index with homeostasis model assessment of insulin resistance in type 2 diabetes mellitus patients, and to determine the association of triglyceride-glucose index with urinary albumin-to-creatinine ratio for predicting diabetic nephropathy. METHODS: The observational, cross-sectional study was conducted from September 2021 to September 2022 at the Department of Chemical Pathology, Pakistan Railway Hospital, Rawalpindi, Pakistan and comprised recently-diagnosed type 2 diabetes mellitus patients. Recorded data included age, gender, vitals, diabetes duration, body mass index and other pertinent demographic and clinical information. Measurements included spot urine albumin-to-creatinine ratio, triglycerideglucose index, homeostasis model assesment of insulin resistance as well as fasting serum insulin, fasting plasma glucose, glycosylated haemoglobin, triglycerides, total cholesterol and serum creatinine. On the basis of triglyceride-glucose index scores, the participants were divided into 4 quartiles; Q1=4.5-5, Q2=5.1-5.5, Q3=5.6-6, and Q4=>6. Data was analysed using SPSS 26. RESULTS: Of the 218 patients, 141(64.7%) were females and 77(35.3%) were males. The overall mean age was 49.22±11.46 years. There were 102(46.8%) overweight patients, 33(15.1%) obese and 82(37.2%) had normal weight. There were 58(26.6%) patients in Q1, 86(39.4%) in Q2, 46(21.1%) in Q3 and 28(12.8%) in Q4. Those in Q4 showed elevated fasting plasma glucose, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and urine albumin-to-creatinine ratio (p<0.05), as well as low values for high-density lipoprotein cholesterol and estimated glomerular filtration rate(p<0.05). Fasting serum insulin was negatively linked to glycated haemoglobin (r=-0.12, p=0.07). Triglyceride-glucose index (r=0.76, p<0.001), homeostasis model assessment of insulin resistance (r=0.48, p<0.001), and urine albumin-to-creatinine ratio (r=0.10,p=0.05) positively correlated with glycated haemoglobin. Fasting serum insulin (r=-0.13, p=0.05), negatively correlated with triglyceride-glucose index, while homeostasis model assessment of insulin resistance (r= 0.32, p<0.001) and urine albumin-to-creatinine ratio (r=0.28, p=0.05) had a positive correlation. The estimated glomerular filtration rate was significantly positively linked with fasting serum insulin (r=0.05, p=0.05), and correlated significantly negatively with triglyceride-glucose index (r=-0.35, p=0.01), homeostasis model assessment of insulin resistance (r=-0.01, p=0.86) and urine albumin-to-creatinine ratio (r=-0.02, p=0.8). CONCLUSIONS: The triglyceride-glucose index showed a strong association with homeostasis model assessment of insulin resistance, and surpassed it in terms of predicting diabetic nephropathy in type 2 diabetes mellitus patients.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study.

BACKGROUND: A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10-8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. RESULTS: Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-ß signalling and Th17 cell differentiation. CONCLUSIONS: Epigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

Amelioration of diabetic nephropathy using pomegranate peel extract-stabilized gold nanoparticles: assessment of NF-κB and Nrf2 signaling system.

BACKGROUND: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer. PURPOSE: This study was designed to investigate the ameliorative role of pomegranate peel extract-stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model. METHODS: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence. RESULTS: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic ß-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis. CONCLUSION: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.

Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus.

Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of <10%, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome ( P for trend <0.001). The hazard ratios were 1.11 (95% CI, 0.97-1.28) for those with an increase of 10% to 19%, 1.34 (1.07-1.66) for 20% to 29%, and 1.44 (1.15-1.81) for ≥30%, compared with <10%. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase ( P for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00145925.

Assessment of Vitamin D-Binding Protein and Early Prediction of Nephropathy in Type 2 Saudi Diabetic Patients.

Early detection of diabetic nephropathy (DN) represents a great challenge in an attempt to reduce the burden of chronic kidney diseases in diabetic patients. This study aimed to investigate the potential early prediction role of urinary vitamin D-binding protein (uVDBP) for the diagnosis of DN and to examine the possible correlation to serum VDBP, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance in these patients. Serum and urine samples were obtained from 40 healthy volunteers and 120 patients with type 2 diabetes divided into 3 groups: normoalbuminuria, microalbuminuria, and macroalbuminuria (urinary albumin excretion rate < 30, 30-300, and >300 µg/mg, resp.); n = 40/group. Serum and urinary VDBP levels were quantified by ELISA. Insulin resistance has been assessed by homeostasis model assessment index (HOMAI). Correction for urine creatinine concentration was applied for urinary quantitative measurements. uVDBP levels were significantly elevated in micro- and macroalbuminuria patient groups compared with those of the normoalbuminuria patient group and controls (820.4 ± 402.8 and 1458.1 ± 210.0 compared with 193.1 ± 141.0 and 127.7 ± 21.9 ng/mg, resp.) (P < 0.001). There was significant correlation between serum and urinary levels of VDBP in total patient group. Receiver operating characteristic analysis of uVDBP levels showed optimum cut-off value of 216.0 ng/mg corresponding to 98.8% sensitivity and 80.0% specificity and an area under the curve of 0.973 to discriminate the normoalbuminuria from the microalbuminuria groups. In multivariate analysis, ordination plot showed obvious demarcation between the study groups caused by the higher levels of uVDBP and albumin/creatinine ratio among other variables. The study findings suggested a possible clinical application of uVDPB as an early and a good marker for the detection of early renal disease in type 2 DM Saudi patients. Large-scale validation studies are warranted to confirm the results before including uVDBP with the available list of other conventional biomarkers.

Why Not to Use the Handgrip Test in the Assessment of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes Mellitus?

OBJECTIVE: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. PATIENTS AND METHODS: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. RESULTS: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (y=0.004, p=0.563), 30/15 ratio (y=0.282, p=0.357), Valsalva ratio (y=-0.058, p=0.436) and orthostatic hypotension (y=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). CONCLUSION: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.

Assessment of glomerular filtration rate based on alterations of serum brain-derived neurotrophic factor in type 2 diabetic subjects treated with amlodipine/benazepril or valsartan/hydrochlorothiazide.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. METHODS: In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. RESULTS: Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r = -0.264, P = 0.021) but not in the 77 subjects treated with benazepril/amlodipine (r = -0.025, P = 0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8 ± 14.9 mL/min/1.73 m(2); P < 0.001). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between -0.887 and -0.076, P = 0.020). CONCLUSIONS: Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril.

Assessment of human cartilage glycoprotein 39 (YKL-40), preptin, and nitric oxide in adolescent patients with type 1 diabetes and its relation to cardiorenal affection.

AIM: To evaluate new biomarkers such as YKL-40, preptin, and nitric oxide (NO) in patients with diabetes and to assess its relation to cardiorenal injury. PATIENTS AND METHODS: The study included 62 patients with type 1 diabetes and 30 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile, YKL-40, preptin, and NO. Also, urine sample was taken for analysis of albumin/creatinine ratio. Echocardiography was also done. RESULTS: NO was lower, whereas YKL-40, preptin, and albumin/creatinine ratio were significantly higher in patients with diabetes. NO had a significant negative correlation with LVEDD, LVESD, PWT, LV mass, YKL-40, preptin, and albumin/creatinine ratio. YKL-40 had a significant positive correlation with waist/height ratio, preptin and negative correlation with E/A ratio. Stepwise multiple regression revealed that E/A ratio is the only parameter related to YKL-40. On the contrary, NO and systolic blood pressure are related to preptin. CONCLUSION: A significant reduction of NO and elevation of YKL-40 and preptin was found in patients with diabetes. A decrease in NO is associated with diastolic dysfunction, LV hypertrophy, and renal impairment, whereas YKL-40 is associated with diastolic dysfunction. An increase in preptin level was associated with hypertension.

Clinical assessment of the autonomic nervous system in diabetes mellitus and its correlation with glycemic control.

AIM: Clinical assessment of the autonomic nervous system in Diabetes mellitus (DM) and its correlation with glycemic control. STUDY DESIGN: Cross sectional study of 50 adult diabetes patients. MATERIALS AND METHODS: Fifty patients with DM who were on regular treatment with either insulin and/or oral hypoglycemic agents were studied. Cardiovascular autonomic neuropathy (CAN) score was calculated using the clinical test variables. RESULTS: Of the 50 patients 30 had no CAN, 10 had early CAN and 10 had severe CAN. The mean of CAN score increased with duration of diabetes. The mean HbA(1C) was 7.73. The mean CAN score was higher in patients who had complication of diabetes as compared to patients without complications. The heart rate variability with respiration was found to be 15.84 ± 7.02/min. The mean valsalva ratio was 1.31 ± 0.23. The mean drop in BP on standing was 7.30 ± 7.24 mmHg. The mean 30:15 ratio was 1.06 ± 0.04. The mean rise in diastolic BP on sustained hand grip was 16.04 ± 4.11 mmHg. CONCLUSIONS: The prevalence of autonomic neuropathy in DM as assessed by CAN score was 40%. The CAN score did not correlate with the duration of DM. The HbA(1C) had a significant correlation with the severity of autonomic neuropathy. Occurrence of CAN correlated with the presence of peripheral neuropathy but not with the presence of retinopathy or nephropathy. All individual tests in the battery of CAN score were significantly associated with the presence of autonomic neuropathy, except 30:15 ratio.

Plasma B-type natriuretic peptide is useful for cardiovascular risk assessment in community-based diabetes subjects: comparison with albuminuria.

Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease. Plasma B-type natriuretic peptide (BNP) levels are elevated in various types of cardiac diseases. Increased plasma BNP levels have been reported to be associated with CV risk in apparently healthy individuals. However, no studies have yet examined the specific value of plasma BNP for predicting CV incidence in unselected DM subjects in a community-based population.In a community-based DM cohort (n = 1,059, mean = 66 years), baseline BNP levels were determined, and CV events were followed and captured prospectively. The cohort was divided by plasma BNP quintiles. The Cox proportional hazard model was used to determine the relative hazard ratios (HR) among the quintiles. In addition, the effects of adding the plasma BNP or urine albumin-to-creatinine ratio (UACR) to an established CV risk scoring model was examined by calculating the area under the receiver operating characteristic (ROC) curve (AUC).During the 5.7 year follow-up period, CV events were identified in 65 of the DM cohort. There was a significant association between plasma BNP levels and CV event rate (P < 0.001). HR was significantly increased in the highest quintile compared to the lowest (HR = 4.38; 95%CI 1.69 -11.84). The AUC generated from ROC analysis of the Framingham risk score for predicting general CV events was improved by adding BNP testing (from 0.66 to 0.74; P = 0.05), but not by adding UACR (from 0.66 to 0.67; P = 0.49).In a community sample of people with DM, plasma BNP levels above the 80 percentile are directly associated with CV risk, and measurement of plasma BNP alone or in conjunction with an established CV risk score is of value in predicting CV events in these subjects.

Assessment of nitrogen radicals and their scavenging activity in patients with end-stage renal failure.

Reactive oxygen species are implicated in cardiovascular disease in patients with chronic renal failure (CRF). This study is aimed to assess the nitrogen radicals in patients with end-stage renal failure (ESRF) referred for peritoneal dialysis. A total of 36 patients with estimated creatinine clearance ≤ 15 mL/min were recruited from the Dialysis Unit at Al-Yarmouk Teaching Hospital in Baghdad, Iraq during 2009, and enrolled into the study. The main causes of CRF were hypertension and diabetes mellitus. The median levels of serum nitric oxide and peroxynitrite were 300 and 152 µmol, respectively. Nitric oxide was not detected in the sera of 10 patients. The sera of 12 patients showed ability to scavenge in vitro, the nitric oxide released by sodium nitroprusside. Significant inverse correlation was found between serum peroxynitrite and either systolic (r = -0.402) or diastolic (r = -0.387) blood pressure. Our study shows that production of nitrogen radicals is enhanced in ESRF and it is accompanied by limited activity of scavenging nitric oxide.

Chronic kidney disease in type 2 diabetes patients in France: prevalence, influence of glycaemic control and implications for the pharmacological management of diabetes.

AIM: Type 2 diabetes mellitus (T2DM) is often associated with chronic kidney disease. For this reason, this article reviews the relationship between treatment of T2DM and renal disease. METHOD: The review presents the recent French data on the management of diabetes in patients with renal impairment, and discusses the implications of renal disease for the treatment of such patients. Prescribing data are presented for various antidiabetic treatments, and the use of the more commonly prescribed medications is discussed with reference to T2DM patients with renal disease. RESULTS: In France, it is estimated that 4-5% of the general population has T2DM and that almost 40% of patients with end-stage renal failure have diabetes. Diabetes and renal disease are both risk factors for cardiovascular morbidity and mortality. Glycaemic control is pivotal in T2DM patients for minimizing the risk of vascular complications and hypoglycaemic episodes, particularly in patients with renal disease who also have a higher risk of hypoglycaemia. Whereas poorly controlled glycaemia increases the risk of renal disease and its progression, the risk is diminished in patients treated intensively for diabetes and in those who achieve stable glycaemic control. Intensive multitargeted treatment can also help to decrease cardiovascular morbidity and mortality, especially if started early in patients who have not yet developed macrovascular complications. CONCLUSION: In recent years, considerable improvement has been observed in France regarding the follow-up of diabetic patients. Less extensive, but nonetheless significant, improvement has also been observed in glycaemic control. However, even though treatment decisions generally take renal function into account, some at-risk treatments are often still being used in patients with renal insufficiency.

National primary care guidelines for England: impact on chronic kidney disease prevention in South Asian populations.

INTRODUCTION: This study evaluated the impact of national policy for kidney disease in primary care comparing South Asian (SA) and white European (WE) population groups. METHODS: Retrospective audits of primary care records of SA and WE adults diagnosed with diabetes in 2004 and 2007 were carried out in a total sample of 707 patients across 18 general practices within Luton, Leicester and West London. RESULTS: Four hundred patients (SA: n=241, and WE: n=159) were diagnosed as diabetic in 2004, and 307 (SA: n=178, and WE: n=129) in 2007. South Asian patients were 9-10 years younger, had lower systolic blood pressure than white Europeans at diagnosis in both years (136.1 vs. 141.4 mm Hg, p=0.01, in 2004; and 134 vs. 142.3 mm Hg, p=0.000, in 2007) and significantly higher HbA1c (8.6%, 63 mmol/L vs. 7.9%, 71 mmol/L) at diagnosis in 2004 than in 2007 (8.3%, 67 mmol/L vs. 8.2%, 66 mmol/L). Recording of the majority of variables associated with diabetic kidney disease increased across both patient groups between 2004 and 2007: albumin to creatinine ratio (up 13.0% in SA to 37.9%, and 15.1% in WE to 40.3%), estimated glomerular filtration rate (up 61.7% in SA to 70.8% and 75.6% in WE to 80.6%) and proteinuria (up 19.3% in SA to 46.3% and 26.1% in WE to 51.9%). CONCLUSIONS: Recording of indicators for diabetic kidney disease at diagnosis increased in both South Asians and white Europeans following introduction of national guidance to improve early detection and quality of care in the diabetic kidney disease care pathway.

Assessment of markers of glycaemic control in diabetic patients with chronic kidney disease using continuous glucose monitoring.

AIM: Due to altered red blood cell survival and erythropoietin therapy glycated haemoglobin (HbA1c) may not accurately reflect long-term glycaemic control in patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA) and fructosamine are alternative markers of glycaemia. The aim of this study was to investigate the accuracy of HbA1c, GA and fructosamine as indicators of glycaemic control using continuous glucose monitoring. METHODS: HbA1c, GA and fructosamine concentrations were measured in 25 subjects with diabetic nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) )) matched with 25 subjects with diabetes and no evidence of nephropathy. Simultaneous real-time glucose concentrations were monitored by continuous glucose monitoring over 48 h. RESULTS: GA correlated significantly to mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P < 0.05). A similar relationship was observed with fructosamine relative to glucose. A poor correlation between HbA1c and glucose was observed with CKD (r = 0.38, P = ns) but was significant in the non-CKD group (r = 0.66, P < 0.001). The GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared with controls (2.5 ± 0.4 vs 2.2 ± 0.4, P < 0.05). HbA1c values were significantly lower in CKD patients, relative to non-CKD patients at comparable mean glucose concentrations. CONCLUSION: HbA1c significantly underestimates glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe CKD, GA more accurately reflects glycaemic control compared with fructosamine and HbA1c and should be the preferred marker of glycaemic control.

Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus.

AIMS: To estimate remaining life expectancy (RLE), quality-adjusted life expectancy (QALE), causes of death and lifetime cumulative incidence of microvascular/macrovascular complications of diabetes for youths diagnosed with Type 2 diabetes. METHODS: A Markov-like computer model simulated the life course for a hypothetical cohort of adolescents/young adults in the USA, aged 15-24 years, newly diagnosed with Type 2 diabetes following either conventional or intensive treatment based on the UK Prospective Diabetes Study. Outcomes included RLE, discounted QALE in quality-adjusted life years (QALYs), cumulative incidence of microvascular/macrovascular complications and causes of death. RESULTS: Compared with a mean RLE of 58.6 years for a 20-year-old in the USA without diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44 discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44 discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence of all microvascular complications and lower mortality from microvascular complications (e.g. end-stage renal disease (ESRD) death 19.4% vs. 25.2%). Approximately 5% with both treatments had ESRD within 25 years. Lifetime cumulative incidence of coronary heart disease (CHD) increased with longer RLE and greater severity of CHD risk factors. Incorporating disutility (loss in health-related quality of life) of intensive treatment resulted in net loss of QALYs. CONCLUSIONS: Adolescents/young adults with Type 2 diabetes lose approximately 15 years from average RLE and may experience severe, chronic complications of Type 2 diabetes by their 40s. The net clinical benefit of intensive treatment may be sensitive to preferences for treatment. A comprehensive management plan that includes early and aggressive control of cardiovascular risk factors is likely needed to reduce lifetime risk of CHD.

Low 25-hydroxyvitamin D levels and mortality in non-dialysis-dependent CKD.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System. PREDICTOR: 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL. OUTCOMES: We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. MEASUREMENTS: 25(OH)D was measured using chemiluminescence immunoassay. RESULTS: Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL. LIMITATIONS: Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias. CONCLUSIONS: 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD.

Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy.

BACKGROUND: Urinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN). METHODS: Fasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy. RESULTS: Urinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r=0.439, P<0.001) and urinary albumin and ALP (r=0.305, P<0.01). Areas under the curve for GGT and ALP were 0.7696 (P<0.001) and 0.7233 (P<0.001), respectively. At a cut-off value of 72U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively. CONCLUSIONS: Urinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP.