The effects of atorvastatin and rosuvastatin on oxidative stress in diabetic patients

Aim

Diabetes is associated with abnormalities in lipid profile and increased oxidative stress. Statins are preferred agents in diabetic patients due to their antioxidant and LDL-C lowering effects. This study is designed to compare the effects of atorvastatin and rosuvastatin on low density lipoprotein cholesterol (LDL-C), lipid hydroperoxide (LOOH), total oxidant status (TOS) and total antioxidant capacity (TAC) in diabetic patients with hyperlipidemia.

Materials and methods

Sixty two patients who have type 2 diabetes mellitus with serum LDL levels more than 100 mg/dL were randomly assigned to receive atorvastatin 20 mg (n = 31) or rosuvastatin 10 mg (n = 31). Blood tests were performed at the beginning of the study and after three months.

Results

There were no statistically significant differences in the pre- and after treatment levels of the LDL-C between groups. TAC values were increased in both groups and statistically significant in the former group (p = 0.007). There was no diferrence between the change percentages ((after treatment TAC − pretreatment TAC) / pretreatment level) of TAC between two treatment groups. The effects of two drugs on the other oxidative parameters were not significantly different.

Conclusion

Both atorvastatin and rosuvastatin may be helpful in reducing increased oxidative stress in diabetic patients with hyperlipidemia.     

Men with hyperferritinemia and diabetes in the Mediterranean area do not have a higher iron overload than those without diabetes

Aim

To assess the role of iron overload in type 2 diabetic men with hyperferritinemia.

Methods

150 men were recruited from a genetic screening programme for hereditary hemocromatosis (HH) and were tested for type 2 diabetes, other components of the metabolic syndrome, beta cell function (BCF), insulin sensitivity, high-sensitivity C-reactive protein and iron overload.

Results

Fifty-one men had type 2 diabetes. They were older (p = 0.017) and 99 had lower BCF (p < 0.001) than non-diabetic men. None of the iron overload indexes was associated with diabetes.

Conclusions

Our findings dispute a role of iron overload in the pathogenesis of type 2 diabetes.     

Protective role of adiponectin on endothelial dysfunction induced by AGEs: a clinical and experimental approach

Objective

Obesity is characterized by low levels of adiponectin, an adipocytes derived hormone, and by an inflammatory component. Endothelial dysfunction is often found in overweight/obesity, diabetes, and atherosclerosis. Advanced glycation end products (AGEs) induce endothelial dysfunction and are linked to diabetes and increased atherogenicity and inflammation. The aim of the study was to investigate the possible link between adiponectin and N(epsilon)-(carboxymethyl) lysine (CML), the predominant adduct of circulating AGEs in overweight patients, and, in an in vitro model, to test the hypothesis that adiponectin acts as modulator of endothelial dysfunction, induced by AGEs.

Results

In 108 overweight patients, plasma levels of CML correlated inversely with adiponectin levels. Pre-incubation of human vein endothelial cells (HUVECs) with physiological concentrations of adiponectin, followed by stimulation with AGEs, reduced vascular adhesion molecule-1 (VCAM-1) and E-selectin expression, as assessed by surface enzyme immunoassay.

Conclusions

Taken together, these findings demonstrate an inverse correlation between CML and adiponectin levels in overweight patients and a protective role of adiponectin on endothelial dysfunction induced by AGEs, suggesting its key role in the treatment of the vascular complications of obesity/metabolic syndrome.     

Reliability and validity of diabetes specific Health Beliefs Model scales in patients with diabetes and serious mental illness

Objective

To study the association of low serum creatinine, abnormal lipid profile and demographic variables with type 2 diabetic Trinidadian subjects.

Methods

Data were obtained from a cohort of 1122 diabetic and non-diabetic patients from clinics in Trinidad. Variables measured included demographics, HbA1_c, serum creatinine, lipid profile values and diabetic status.

Results

The sample consisted of 476 males (61.6% diabetic) and 646 females (50.3% diabetic). Most patients (59.2%) were Indo-Trinidadian, 23.4% were Afro-Trinidadian and 13.5% were of ‘mixed’ and ‘other’ categories. The majority (55.1%) of the patients were diabetic and diabetics were older than non-diabetics (p = 0.000). Abnormal lipid profile OR = 0.728, CI (0.532, 0.994), serum creatinine categories OR = 1.520, CI (1.317, 1.754), gender OR = 0.690, CI (0.533, 0.892) and age groups OR = 1.305, CI (1.185, 1.437) were useful predictors of type 2 diabetes. Ethnicity was not a useful predictor: OR = 1.007, CI (0.869, 1.168). Serum creatinine (mean) was found to be lower in diabetics aged 21-50 than in their non-diabetic counterparts. However, above 50 years old, the reverse was true. Serum creatinine means were higher in males than in females (p = 0.000).

Conclusion

Abnormal lipid profile, gender, age and serum creatinine are associated with type 2 diabetes. While age and gender are non-modifiable risk factors, steps should be taken to monitor and control the serum creatinine and lipid profile values of diabetics and non-diabetics.     

Insulin resistance index (HOMA-IR) levels in a general adult population: curves percentile by gender and age. The EPIRCE study

Aims

To describe the distribution of HOMA-IR levels in a general nondiabetic population and its relationships with metabolic and lifestyles characteristics.

Methods

Cross-sectional study. Data from 2246 nondiabetic adults in a random Spanish population sample, stratified by age and gender, were analyzed. Assessments included a structured interview, physical examination, and blood sampling. Generalized additive models (GAMs) were used to assess the effect of lifestyle habits and clinical and demographic measurements on HOMA-IR. Multivariate GAMs and quantile regression analyses of HOMA-IR were carried out separately in men and women.

Results

This study shows refined estimations of HOMA-IR levels by age, body mass index, and waist circumference in men and women. HOMA-IR levels were higher in men (2.06) than women (1.95) (P = 0.047). In women, but not men, HOMA-IR and age showed a significant nonlinear association (P = 0.006), with increased levels above fifty years of age. We estimated HOMA-IR curves percentile in men and women.

Conclusions

Age- and gender-adjusted HOMA-IR levels are reported in a representative Spanish adult non-diabetic population. There are gender-specific differences, with increased levels in women over fifty years of age that may be related with changes in body fat distribution after menopause.     

Time-dependent impact of diabetes on the mortality of patients on renal replacement therapy: a population-based study in Germany (2002-2009)

Aims

To estimate the impact of diabetes on the mortality of patients with incident renal replacement therapy (RRT).

Methods

We assessed the mortality of 544 incident RRT patients aged ≥30 years between 2002 and 2009 (57.9% men, mean age 70.3 years, 49.6% patients with diabetes) by analyzing the data of all dialysis centers covering a German region. We compared the estimated time-dependent hazard ratios of patients with and without diabetes by using the Cox proportional-hazards regression model.

Results

Overall, 319 patients had died (158 diabetic), approximately 50% after 3 years. Up to about 3 years, the mortality rate was lower in diabetic than in nondiabetic patients. Thereafter, the survival curves crossed (interaction diabetes × time, p = 0.002; adjusted hazard ratios for diabetes: baseline, 0.66; year 1, 0.84; year 2, 1.05; year 3, 1.33; year 4, 1.68). The results were similar in men and women; however, the interaction of diabetes and time was significant only in men (p = 0.004). Further significant risk factors of mortality were age, sex, initial central venous catheter, cardiovascular disease, and malignancy.

Conclusions

In this population-based study, the influence of diabetes was time-dependent, with a lower mortality in diabetic versus non-diabetic patients in the first three years but a higher mortality in these patients after 3 years. Results were similar in men and women.     

Mortality, incidence of cardiovascular diseases, and educational level among the diabetic and non-diabetic populations in two large Italian cities

Aims

We investigated if diabetes modifies the effect of the association of education with mortality and incidence of cardiovascular diseases.

Methods

We identified 44,889 diabetics using multiple data sources. They were followed up from January 2002 up to December 2005, and their mortality, incidence of myocardial infarction and stroke, by educational level were analysed, and compared with those of the local non-diabetic population.

Results

The all-cause Standardized Mortality Ratios among diabetics, compared with non-diabetics, were 170 for men and 175 for women. Standardized Incidence Ratios were 199 for myocardial infarction, and 183 for stroke in men and, respectively, 281, and 179 in women. Among non-diabetics there was a clear inverse relation with educational level for all outcomes, whereas among diabetics no significant social difference in incidence was found; slight social differences in mortality were present among men, but not among women. The effect of diabetes on social differences was enhanced in the youngest population.

Conclusions

Diabetes increases the risk of death and the incidence of vascular diseases, but reduces their inverse association with education. This is likely related to the high accessibility and good quality of health care provided by the local networks of diabetic centres and primary care.     

Does instant coffee prevent acute liver injury induced by carbon tetrachloride (CCl4)?

Objective

To investigate the protective effect of instant coffee (IC) on acute liver injury induced by CCl₄.

Methods

The study included 32 rats which were allocated to four groups: control (n: 8), CCl₄ (n: 8), CCl₄ + IC (n: 8) and IC (n: 8). Malondialdehyde, which is a lipid peroxidation product, and levels of antioxidant capacity were measured and histopathological data were compared.

Results

It was seen in the study that lipid peroxidation products that increased in the plasma and liver tissue of the CCl₄ group decreased by IC administration. There was an increase in the measured antioxidant parameters, which were total antioxidant capacity (TAOC), sulphydryl (SH) and ceruloplasmin levels. Histopathologically, it was found that inflammation and necrosis which increased in the group administered CCl₄ decreased significantly with IC administration, but there steatosis did not change.

Conclusions

It was seen that IC had a protective role in acute liver injury induced by CCl₄, but did not affect steatosis.     

Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: A role for Nrf2 in vascular protection in diabetes

Background and aims

Hyperglycemia and diabetes are associated with increased formation of advanced glycation end products and enhanced oxidative stress, leading to the progression of diabetic vascular disease. We have investigated the mechanisms by which AGE-modified bovine albumin (AGE-BSA) induces reactive oxygen species (ROS) generation, leading to nuclear factor-erythroid 2-related factor (Nrf2) dependent induction of the antioxidant genes heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase 1 (NQO1) in bovine aortic endothelial cells.

Methods and results

AGE-BSA (100 μg ml⁻¹, 0-24 h), but not native BSA, elicited time-dependent increases in ROS generation, Nrf2 nuclear translocation and enhanced mRNA and protein expression of HO-1 and NQO1, but not glutathione peroxidase-1. Inhibition of ROS production with the superoxide scavenger Tiron or inhibitors of flavoproteins (diphenylene iodonium) and NADPH oxidase (apocynin), but not eNOS (l-NAME) or mitochondria complex I (rotenone) abrogated HO-1 induction by AGE-BSA. Although AGE-BSA induced rapid phosphorylation of JNK and Akt, only inhibition of JNK abrogated HO-1 expression, implicating the involvement of the JNK signaling pathway in AGEs activation of Nrf2/ARE-linked antioxidant gene expression.

Conclusion

Our findings establish that AGEs activate redox sensitive Nrf2-dependent antioxidant gene expression in bovine aortic endothelial cells, providing an adaptive endogenous defense against oxidative stress in diabetes.     

High-risk diabetic nephropathy patients: the outcome of evidence-based clinical practice in an outpatient clinic

Objective

A retrospective audit to assess the impact of a combined diabetes-renal consultant clinic over 10 years, on slowing the progression of diabetic nephropathy, using recognised markers of renal disease progression, including creatinine clearance and proteinuria.

Methods

44 high-risk patients with diabetic nephropathy defined as having significant proteinuria (an elevated albumin creatinine ratio greater than 30 mg/mmol), and hypertension, a progressive rise in plasma creatinine or other evidence of diabetic microvascular disease or macrovascular disease, were identified. Sufficient follow up was defined as at least two data sets over a 12-month period prior to referral to the combined clinic, and at least 18 months of combined clinic follow up thereafter.

Results

In this high risk group, GFR was falling at an average of 7.97 m/min/year (95% CI 9.83-6.10 ml/min/year) at the time of referral and following clinic intervention this was significantly reduced to 3.17 ml/min/year (95% CI 4.47-1.87 ml/min/year) over the duration of follow up. Blood pressure, glycaemic control and lipid status remained stable and close to current recommended guidelines.

Conclusions

A combined diabetes-renal consultant clinic is an effective intervention to improve the outcome of high-risk diabetics with progressive diabetic nephropathy.     

Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage

Objective

To determine the efficacy of pazopanib eye drops in the streptozotocin induced diabetic retinopathy rat model.

Methods

A 0.5% w/v pazopanib suspension was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5% w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three groups (n = 4) — (1) healthy, (2) diabetic, and (3) diabetic with treatment. The drug suspension was administered twice daily as eye drops to group 3 for 30 days. Efficacy parameters including the number of adherent leukocytes in the retinal vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to-plasma protein ratio were measured.

Results

Pazopanib suspension in the form of eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%), and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to untreated diabetic group.

Conclusion

Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.     

Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients

Aims

Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines.

Methods

79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed.

Results

In multiple regression ICAM-1 (p = 0.004) and adiponectin (p = 0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p = 0.03, r = 0.24).In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p = 0.02). Urinary MCP-1 did not correlate to uACR.

Conclusions

In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.     

Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats

Aims

Stem cells are a new hope to ameliorate impaired diabetic wound healing. The purpose of this study was to evaluate the effect of adipose tissue derived mesenchymal stem cells (AD-MSCs) on wound healing in a diabetic rat model.

Methods

Twenty-six rats became diabetic by a single intraperitoneal injection of streptozotocin. Six rats served as non-diabetic (non-DM). Diabetic rats were divided into two equal groups randomly; control and treatment. Six weeks later, a full-thickness circular excisional wound was created on the dorsum of each rat. AD-MSCs were injected intra-dermally around the wounds of treatment group. PBS was applied to control and non-DM groups. The wound area was measured every other day. After wound healing completion, full thickness skin samples were taken from the wound sites for evaluation of volume density of collagen fibers, length and volume density of vessels, and numerical density of fibroblasts by stereological methods.

Results

AD-MSCs accelerated wound healing rate in diabetic rats, but did not increase length and volume density of the vessels and volume density of the collagen fibers. AD-MSCs decreased the numerical density of fibroblasts.

Conclusions

We concluded that AD-MSCs enhances diabetic wound healing rate probably by other mechanisms rather than enhancing angiogenesis or accumulating collagen fibers.     

Elevated micronuclei frequency in type 2 diabetes with high glycosylated hemoglobin

Aim

The role of oxidative damage to DNA due to hyperglycemia is well known. In the current study we have evaluated the induction of micronuclei due to increased glycosylation in type 2 diabetes.

Methods

Forty-nine subjects divided into two groups of normoglycemic controls and type 2 diabetic cases were recruited in the study. Whole blood was cultured and micronuclei were scored in all the cases. This was correlated with age, sex, blood glucose levels and glycosylated hemoglobin.

Results

Age and sex matched diabetic patients had an increased micronuclei frequency in response to elevated glycosylation of hemoglobin (R² = 0.229, p = 0.037) compared to normoglycemic subjects.

Conclusion

The increased glycosylation seems to induce oxidative damage in the DNA of the diabetic patients, which manifests as an increased micronuclei frequency. This has a potential to be used as a biomarker for subsequent diabetic complications.     

Epstein Barr virus hepatitis

Objectives

Epstein-Barr Virus (EBV) infection has the potential to establish life-long, benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis.

Patients and methods

All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied.

Results

The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotrasferase (AST) and alanine-aminotrasferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%).

Conclusion

Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.     

Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients

Aim

Chemerin, a new adipocytokine, has been suggested to be linked to obesity-induced insulin resistance and type 2 diabetes. The association of plasma chemerin levels with diabetic nephropathy, however, is unknown. Therefore, this study aims to determine whether plasma chemerin levels are associated with renal function in type 2 diabetic patients.

Methods

A total of 116 type 2 diabetic patients and 38 healthy subjects were enrolled in this study. Serum levels of chemerin were measured by enzyme-linked immunosorbent assay.

Results

Serum chemerin was significantly elevated in type 2 diabetic patients with macroalbuminuria compared with control subjects and diabetic patients with normoalbuminuria and microalbuminuria. No differences were found in the level of serum chemerin between diabetic patients with normoalbuminuria and microalbuminuria and control subjects. Serum chemerin was positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine and serum triglycerides, and negatively correlated with creatinine clearance Stepwise regression analysis showed that creatinine clearance and serum creatinine remained significantly associated with serum chemerin.

Conclusion

Serum chemerin levels are strongly associated with renal function in diabetic patients.     

Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications

Aims

To test autoantibodies from subsets of diabetes with painful neuropathy, maculopathy and nephropathy for effects in neurons.

Methods

Protein-A eluates from plasma of 27 diabetic and 19 age-matched controls were tested for effects on endothelial cell survival, and neurite outgrowth in rat pheochromocytoma PC12 cells. Painful diabetic neuropathy or control autoantibodies were compared for binding to PC12-derived heparan sulfate proteoglycans. The mechanism of the effects from pathologic autoantibodies was investigated by changes in intracellular calcium in endothelial cells, whole cell current in neurons, or using the Rho kinase inhibitor Y27632.

Results

Autoantibodies from diabetic patients with maculopathy, nephropathy, and painful neuropathy (n = 5) caused significantly greater mean inhibition of neurite outgrowth (p < 0.005) than diabetic or control patients with fewer or no complications (n = 30). Painful diabetic autoantibodies (3 μg/mL) bound neuronal heparan sulfate proteoglycan (HSPG) more than autoantibodies from diabetic or control subjects without painful neuropathy (p < .0001). Inhibition of PC12 neurite outgrowth by the painful neuropathy antibodies was completely prevented by 1 μM concentrations of Y27632.

Conclusion

These results suggest anti-endothelial and anti-neuronal effects from auto-antibodies in a subset of diabetic patients with a cluster of microvascular complications.     

Erythrocyte Na+-Li+ counter-transport activity and digoxin-like substances in insulin dependent diabetic women with preexisting preeclampsia

Aim of the study

To determine whether there is pathogenetic link between red cells sodium-lithium counter-transport activity and digoxin-like immunoreactive substances (DLIS) in plasma of insulin-dependent diabetic (IDDM) and non-diabetic women with preexisting preeclampsia (PE).

Subjects and methods

We studied Na⁺/Li⁺ CT activity in red cells and plasma levels of DLIS in 11 IDDM women with preexisting PE (Group 1), 13 IDDM without preexisting PE (Group 2) 23 non-diabetic women with preexisting PE (Group 3) and 12 non-diabetic women with normal pregnancy (Group 4) at least 4 months after delivery.

Results

Na⁺/Li⁺ CT activity was higher in Group 1 compared to Group 2 (mean ± SEM 0.316 ± 0.05 vs 0.190 ± 0.02 mmol/LRBC/hr p < 0.05) and in Group 3 compared to Group 4 (0.365 ± 0.004 vs 0.168 ± 0.01 mmol/LRBC/hr, p < 0.01). Plasma levels of DLIS were higher in Group 3 compared to Group 4 (0.727 ± 0.189 vs 0.295 ± 0.066 ng/ml; p < 0.05); there was no statistically significant difference between the two diabetic groups. In Groups 1 and 3, Na⁺/Li⁺ CT activity was correlated to the plasma levels of DLIS (r = 0.927; p < 0.001 and r = 0.485; p < 0.05 respectively).

Conclusion

Increased Na⁺/Li⁺ CT activity and increased plasma levels of DLIS may contribute to PE in IDDM and non-diabetic women.     

Metabolic syndrome and the development of type 2 diabetes among professionals living in Beijing, China

Aims

The magnitude of the association between metabolic syndrome (MetS) and incident diabetes is still not widely evaluated in China. This study explored the association of MetS and its components with the development of diabetes among professionals living in Beijing.

Methods

Population-based 6-year prospective study. The cohort consisted of 7922 eligible persons aged ≥20. Either fasting glucose (FPG) level ≥7.0 mmol/l at the follow-up survey or diagnoses of diabetes during the 6-year period were considered incident diabetes cases. MetS was identified by both the definitions proposed by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF).

Results

The accumulated incidence of diabetes was 3.6% for men and 2.5% for women. MetS associated a 4.7- and 5.7-fold increase of the diabetic risk in men and women, respectively. Hyperglycemia exhibited the highest association with diabetes. FPG of 5.6-5.79 mmol/l already presented a risk of diabetes. However, without hyperglycemia in the clustering of any 1, 2, 3 to 4 metabolic components, the tendency of increased diabetic risk was still observed.

Conclusions

MetS has a strong association with incident diabetes. Of the individual components, hyperglycemia is the strongest predictor of diabetes. Additional numbers of metabolic components increase the risk of developing diabetes.     

Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease

Aims

We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally.

Methods

The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008.

Results

Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD.

Conclusions

Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia.