Subsequent Diabetic Nephropathy Research Articles

Analysis of the Incidence of Type 2 Diabetes, Requirement of Insulin Treatment, and Diabetes-Related Complications among Patients with Cancer

This retrospective nationwide population-based cohort study used a dataset collected from the Korean National Health Insurance Service. We evaluated incident type 2 diabetes, insulin requirements, and diabetes-associated complications during a 10-year follow-up period using the log-rank test and Cox proportional hazards regression models. In total, 8114 and 16,228 individuals with and without cancer, respectively, were enrolled. We found a higher incidence rate and an increased adjusted hazard ratio (HR) for new cases of type 2 diabetes in patients with cancer, compared with those without cancer. Additionally, patients with cancer had a higher risk of insulin requirement than patients without cancer (adjusted HR 1.43, 95% confidence interval [CI], 1.14-1.78). Although there was no significant association between diabetes-associated complications and overall cancer diagnosis, specific cancer types (pancreas, bladder, and prostate) showed an increased risk of subsequent diabetic nephropathy. Therefore, clinicians should closely monitor patients with cancer for the early detection of type 2 diabetes and related morbidities.

The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.

English

BACK GROUND: The objective of this study is to estimate microalbumin in type - 2 diabetes mellitus patients. METHODS: The sensitive marker for the detection of urine albumin excretion was done by estimation of morning urine sample by semi quantitative procedure by Bayerclinitek50 urine chemistry analyzer. For creatinine jaffes method, fasting blood sugar and post lunch blood sugar were estimated by glucometer and glycosylated hemoglobin (HbA1c) was analyzed by Merck microlab 120 semi -automated analyzer. RESULTS: In the study significant increase in micro albumin was observed 193.50 ± 73.66 (P<0.0001) in all the patients of type 2 diabetes mellitus which is the predictor of late development diabetic nephropathy. Para meters like fasting blood sugar, post lunch blood sugar, creatinine and glycosylated hemoglobin (HbA1c) levels were increased above the normal range. CONCLUSION: In type 2 diabetes, microalbumin is the hallmark of subsequent diabetic nephropathy and a surrogate marker of cardiovascular diseases and increased cardiovascular mortality. In diabetic nephropathy patients, glomerular filtration rate is increased in early stage of the disease and glomerulopathy is an important renal structural change. Improving glycemic control in patients with type 2 diabetes may subsequently reduce the risk of complications.

Dual Blockade of the Renin-Angiotensin System in Diabetic Nephropathy

The accelerated progression of atherosclerosis in diabetes is most probably the end result of the cumulative impact of the major risk factors that are more prevalent in diabetic subjects, namely obesity and dyslipidemia, the derangement in carbohydrate metabolism (hyperglycemic environment, hyperinsulinism, and insulin resistance), a prothrombotic tendency, and, perhaps most important, microalbuminuria and hypertension (1–5). At least two additional cardiovascular risk factors are probably more pronounced in diabetes; they are endothelial dysfunction (6) and an inflammatory reaction in the affected blood vessels mediated by the proinflammatory interleukins and expressed by elevated levels of C-reactive protein (7). Microalbuminuria is often the first clinical manifestation of early microvascular derangement. In type 2 diabetes, it is the hallmark of subsequent diabetic nephropathy and a surrogate marker of cardiovascular disease and increased cardiovascular mortality (8). Furthermore, the presence of microalbuminuria predicts a worse outcome after percutaneous coronary intervention. The 2-year mortality after percutaneous coronary intervention in diabetic patients with microalbuminuria was increased by 85% compared with individuals with normal urinary albumin excretion (9). Microalbuminuria is associated with echocardiographic evidence of left ventricular hypertrophy and identifies overall cardiovascular risk also in hypertensive nondiabetic patients (10,11). It is therefore mandatory to screen all diabetic as well as nondiabetic hypertensive patients for the presence of microalbuminuria. Indeed, all the relevant professional associations have included annual screening for microalbuminuria in their recommendations (12,13). Treatment strategies aimed at reducing urinary albumin excretion were found to be effective in retarding the progression of renal disease, as manifested by prolongation of the time to doubling of serum creatinine and postponement of end-stage renal disease and the need to renal replacement therapy (14–17). Furthermore, the magnitude of early decline in albuminuria in response to a given therapeutic intervention is a reliable predictor …

Increased glomerular cytosolic phospholipase A2 activity of OLETF rats with early diabetes.

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A2 (cPLA2), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30-46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA2 activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA2 activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA2 activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.

Renal hemodynamic changes and renal functional reserve in children with type I diabetes mellitus

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 +/- 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 +/- 22.9 vs. 124.8 +/- 25 ml/min per 1.73 m(2)), whereas renal plasma flow was significantly lower (463.7 +/- 103.9 vs. 587.2 +/- 105 ml/min per 1.73 m(2), p < 0.001), and filtration fraction was increased (29 +/- 8 vs. 21 +/- 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (-0.77 +/- 23 vs. 21 +/- 8 ml/min per 1.73 m(2)). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.

Prediction of Diabetic Nephropathy Using Urine Proteomic Profiling 10 Years Prior to Development of Nephropathy

We examined whether proteomic technologies identify novel urine proteins associated with subsequent development of diabetic nephropathy in subjects with type 2 diabetes before evidence of microalbuminuria. In a nested case-control study of Pima Indians with type 2 diabetes, baseline (serum creatinine <1.2 mg/dl and urine albumin excretion <30 mg/g) and 10-year urine samples were examined. Case subjects (n = 31) developed diabetic nephropathy (urinary albumin-to-creatinine ratio >300 mg/g) over 10 years. Control subjects (n = 31) were matched to case subjects (1:1) according to diabetes duration, age, sex, and BMI but remained normoalbuminuric (albumin-to-creatinine ratio <30 mg/g) over the same 10 years. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was performed on baseline urine samples, and training (14 cases:14 controls) and validation (17:17) sets were tested. At baseline, A1C levels differed between case and control subjects. SELDI-TOF MS detected 714 unique urine protein peaks. Of these, a 12-peak proteomic signature correctly predicted 89% of cases of diabetic nephropathy (93% sensitivity, 86% specificity) in the training set. Applying this same signature to the independent validation set yielded an accuracy rate of 74% (71% sensitivity, 76% specificity). In multivariate analyses, the 12-peak signature was independently associated with subsequent diabetic nephropathy when applied to the validation set (odds ratio [OR] 7.9 [95% CI 1.5-43.5], P = 0.017) and the entire dataset (14.5 [3.7-55.6], P = 0.001), and A1C levels were no longer significant. Urine proteomic profiling identifies normoalbuminuric subjects with type 2 diabetes who subsequently develop diabetic nephropathy. Further studies are needed to characterize the specific proteins involved in this early prediction.

Hypertension and antihypertensive treatment of diabetic nephropathy

We are currently confronted with an epidemic of renal failure caused by diabetic nephropathy. It has become apparent that blood pressure is a major determinant of the risk of developing diabetic nephropathy; individuals with a genetic predisposition to hypertension are at increased risk of developing diabetes and diabetic nephropathy. Antihypertensive medication has an impact on development of diabetes; beyond blood-pressure lowering, the risk of diabetes is further reduced by blockade of the renin-angiotensin system (RAS). In experimental studies, blockade of the RAS in the pre-diabetic stage ameliorates the severity of subsequent diabetic nephropathy. Guidelines recommend a target blood pressure of 130/80 mmHg for diabetic patients without proteinuria and some guidelines recommend a target of less than 125/175 mmHg for diabetic patients with proteinuria. Above a systolic blood pressure of approximately 110 mmHg, the risk of progression of diabetic nephropathy increases progressively with increasing blood pressure. Blood-pressure lowering and blockade of the RAS delays or prevents onset of microalbuminuria, slows worsening of microalbuminuria and attenuates progression of diabetic nephropathy, even in advanced stages. In addition to blood pressure, proteinuria is a treatment target and should be reduced to below 1 g/24 h.

On the prognosis of IDDM patients with large kidneys.

Approximately 10-30% of IDDM patients develop diabetic nephropathy depending on the metabolic control. Previous examinations on the significance of the kidney size prior to the manifestation of nephropathy produced varying results. The present study, therefore, was designed to assess the correlation between sonographically determined kidney size and kidney function over 8 years in a follow-up examination, and to evaluate a potential risk pattern. Data could be collected from 73 (66%) of 110 IDDM patients with initially normal serum creatinine whose sonographically determined kidney volume (cm3 = L cm x W cm x D cm x pi/6) and kidney function (creatinine, albuminuria, beta2-microglobulin in serum) had been examined in 1986, and who had a diabetes duration of 1 month to 25 years at that time. 30% (11 of 37) patients with large kidneys (>170 cm3) reached at least one serious renal end-point (increase of serum creatinine by more than 50%, requirement of dialysis or kidney transplantation, or death in end-stage renal disease) versus one of 36 patients with normal kidney size (P<0.002). As many as 42% of patients with large kidneys developed abnormal creatinine values (>106 micromol/l) in contrast to only 20% of the patients with normal kidney volume (P<0.05). Six of seven patients with a more than 50% increase of serum creatinine from baseline showed large kidneys in 1986, but had a normal serum creatinine, and four also a normal urine albumin excretion. Furthermore all five patients with more severe end-points (two deaths in end-stage renal disease and three patients presently requiring dialysis) exhibited either an increased serum creatinine or large kidneys at baseline; four of these, however, were still in the normoalbuminuric state in 1986. These results indicate that large kidneys might be a morphological marker for subsequent diabetic nephropathy, and as a consequence, renal insufficiency.