Diabetic Kidney Disease Without Albuminuria: A New Entity in Diabetic Nephropathy.

Non-albuminuric diabetic kidney disease (NA-DKD) is characterized by progressive loss of kidney function with an annual loss of estimated glomerular filtration rate (eGFR) more than 3 mL/ min/ 1.73m2 per year. NA-DKD is also associated with the late manifestation of diabetic kidney disease, characterized by reduced eGFR (< 60 mL/min/ 1.73m2), in the absence of albuminuria (urine albumin-to-creatinine ratio [UACR] less than 30 mg/g. The typical glomerular changes seen in diabetic nephropathy are less frequently observed in normoalbuminuric patients, while they predominantly show mesangial expansion and tubulointerstitial and vascular changes. The prevalence of NA-DKD has been increasing during the past decade, with a wide range of prevalence in different studies. It seems that patients with NA-DKD are more likely to be female and have better metabolic profile including a lower Hb A1c, lower triglyceride, lower cholesterol, lower BMI and systolic blood pressure, and lower rate of retinopathy. Compared to patients with albuminuria, those with NA-DKD show a lower risk for progression to end-stage kidney disease (ESKD), or rapid decline in eGFR. They also have increased risks of death and hospitalization for heart failure compared with non-DKD diabetic patients, but a lower risk in comparison with albuminuric DKD, regardless of GFR. There is no effective treatment for this phenotype of the disease, but limited data support the use of SGLT2 inhibitors to slow chronic kidney disease progression along with appropriate metabolic risk factor control. More clinical research and pathologic studies are needed for a better understanding of the phenotype, prevention, and treatment methods of the disease.  DOI: 10.52547/ijkd.7966.

Determinants of the progression to type 2 diabetes and regression to normoglycemia in people with pre-diabetes: A population-based cohort study over ten years.

AIMS: To determine the rates and predictors of the regression to normoglycemia and progression to diabetes among subjects with pre-diabetes. METHODS: A 10-year longitudinal population-based study was conducted among 1329 participants with pre-diabetes in the Tehran Lipid and Glucose Study. Pre-diabetes was divided into isolated IFG (iIFG), isolated IGT (iIGT), and combined IFG/IGT. Univariate and stepwise multivariable Cox regression was used to evaluate predictors of glycemic conversions. RESULTS: The cumulative incidences of normoglycemia and diabetes were 43.7% (95%CI 40.9-46.4) and 40.1% (37.3-42.7), respectively. Isolated IGT returned to normoglycemia more than iIFG (HR:1.26, 1.05-1.51), but there was no difference in how quickly they progressed to diabetes. Regression to normoglycemia was associated with younger age, female sex, lower BMI, no familial history of diabetes, higher HDL-C, and ex-smoking. Older age, higher BMI, diastolic blood pressure, total cholesterol, lower HDL-C, and familial history for diabetes were associated with progression to diabetes. The influence of BMI on glycemic status conversions diminished with age. At approximately above 60 years old, the hazards of BMI for any conversions faded out. CONCLUSIONS: The modifiable predictors of regression to normoglycemia and progression to diabetes are roughly the same. The importance of BMI attenuates in elderly subjects.

Patterns of change in obesity indices and other cardiometabolic risk factors before the diagnosis of type 2 diabetes: two decades follow-up of the Tehran lipid and glucose study.

BACKGROUND: Identifying patterns of variation in obesity indices and other cardiometabolic risk factors before the diagnosis of type 2 diabetes could provide insight into the critical period when drastic changes occurred and facilitate targeted interventions for the prevention of diabetes. Therefore, this study sought to explore patterns of change in obesity indices and other cardiometabolic risk factors before diabetes diagnosis. METHODS: We investigated 6305 participants (43.7% men) aged 20-65 from the Tehran Lipid and Glucose Study (TLGS) who were free of diabetes at baseline. First, we jointly estimated developmental multi-trajectories of obesity indices using multivariate latent class growth mixed model, and then patterns of cardiometabolic risk factors within the identified multi-trajectories were assessed using mixed-effects models. RESULTS: Three patterns of change in obesity indices were identified. Most participants belonged to the "progressing" group (83.4%; n = 742), with a slight but steadily rising in obesity indices until diagnosis in both men and women. All multi-trajectory groups showed similar exponential increases in fasting and 2-h plasma glucose concentrations 6 years before diagnosis and linear increases in blood pressure and total and LDL cholesterol throughout follow-up. Patterns of triglyceride and HDL cholesterol accompanied each group's patterns of change in obesity indices. CONCLUSION: Three patterns of the joint progression of obesity indices before diabetes diagnosis were accompanied by similar blood glucose patterns and other cardiometabolic risk factors. These findings suggest the impact of the increasing trend of obesity indices and other metabolic factors on the incidence of diabetes and emphasize the importance of assessing the metabolic risk factors at each visit.

miRNA-148b and its role in various cancers.

miRNA-148b belongs to the family miR-148/-152, with significant differences in nonseed sequences, which can target diverse mRNA molecules. Reportedly, it may undergo deregulation in lung and ovarian cancers and downregulation in gastric, pancreatic and colon cancers. However, there is a need for further studies to better characterize its mechanism of action and in different types of cancer. In this review, we focus on the aberrant expression of miR-148b in different cancer types and highlight its main target genes and signaling pathways, as well as its pathophysiologic role and relevance to tumorigenesis in several types of cancer.

Lay abstract miRNA-148b, or miR-148b, is a tumor suppressor that can regulate invasion-, apoptosis- and proliferation-related oncogenes. miR-148b prognostic and diagnostic potential has been the center of focus recent investigations and extensive studies have been performed on miR-148b regulation in carcinogenesis. Here, we review the role of miR-148b in various cancers and its potential therapeutic application as a target or biomarker.

Trajectories of cardiovascular disease risk and their association with the incidence of cardiovascular events over 18 years of follow-up: The Tehran Lipid and Glucose study.

BACKGROUND: Understanding long-term patterns (trajectories) of cardiovascular diseases (CVD) risk and identifying different sub-groups with the same underlying risk patterns could help facilitate targeted cardiovascular prevention programs. METHODS: A total of 3699 participants of the Tehran Lipid and Glucose Study (TLGS) (43% men, mean age = 53.2 years), free of CVD at baseline in 1999-2001 and attending at least one re-examination cycle between the second (2002-2005) and fourth cycles (2009-2011) were included. We examined trajectories of CVD risk, based on the ACC/AHA pooled cohort equation, over ten years and subsequent risks of incident CVD during eight years later. We estimated trajectories of CVD risk using group-based trajectory modeling. The prospective association of identified trajectories with CVD was examined using Cox proportional hazard model. RESULTS: Three distinct trajectories were identified (low-low, medium-medium, and high-high risk). The high-high and medium-medium CVD risk trajectories had an increasing trend of risk during the time; still, this rising trend was disappeared after removing the effect of increasing age. Upon a median 8.4 years follow-up, 146 CVD events occurred. After adjusting for age, the medium-medium and high-high trajectories had a 2.4-fold (95% CI 1.46-3.97) and 3.46-fold (95% CI 1.56-7.70) risk of CVD compared with the low-low group, respectively. In all trajectory groups, unfavorable increasing in fasting glucose, but favorable raising in HDL and decreasing smoking and total cholesterol happened over time. CONCLUSIONS: Although the risk trajectories were stable during the time, different risk factors varied differently in each trajectory. These findings emphasize the importance of attention to each risk factor separately and implementing preventive strategies that optimize CVD risk factors besides the CVD risk.

Metabolic risk factors among prediabetic individuals and the trajectory toward the diabetes incidence.

BACKGROUND: This study investigates the trajectory of the risk factors of prediabetes progression to overt diabetes. METHODS: The study retrospectively investigated 1610 prediabetic individuals. The trajectory of metabolic indicators was investigated using the generalized estimated equation method with autoregressive working correlation structure through a linear model with the identity link function. RESULTS: During 15 years of follow-up, the trajectories of metabolic risk factors changed from 3 years before diabetes occurrence for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG), 6 years for waist circumference (WC), 9 years for high-density lipoprotein cholesterol (HDL-C), and earlier for body mass index, triglyceride (TG), and TG:HDL ratio. It was shown that the differences in the trajectory of WC and HDL were stable after adjustment for other metabolic risk factors. The trajectories of FPG and 2hPG remained stable after considering multiple insulin resistance markers. CONCLUSIONS: Deterioration of metabolic risk factor status can be a predictor of diabetes many years before its occurrence, but the abrupt change in plasma glucose is evident 3 years before diabetes mellitus onset. It seems that the HDL-C and WC trajectories are two independent predictors for diabetes incidence. It was also found that when the rising trend in plasma glucose starts, preventive strategies to lessen insulin resistance might not be efficient.

Relative frequency of Human T-cell Lymphotropic Virus I/II in HIV/AIDS patients.

BACKGROUND: Human T-cell lymphotropic virus HTLV-I/II is a retrovirus that has been associated with different diseases. HTLV-I/II routes of transmissions are exposure to contaminated blood, blood transfusion, needle sharing, breast feeding, and sexual contact. The seroprevalence of HTLV-I/II in HIV infected patients has not been well characterized in Iran. We conducted a serological survey to determine the relative frequency of HTLV-I/II in HIV+/AIDS and healthy blood donors in Isfahan. MATERIALS AND METHODS: In this cross-sectional study, we compare the relative frequency of HTLV-I/II in HIV+/AIDS group (56 persons) with asymptomatic blood donors (57 persons) in Isfahan. Participant completed the questionnaires that include demographic information, age, sex, and sexual partnership during last 6 months, sexual behavior and past history of blood transfusion or other blood products. We confirm the HIV+ status in patients group with western blot test. Evaluation of HTLV-I/II were done using ELISA test with DRAPIO third generation kit. Questionnaire data and laboratory results were analyzed by SPSS18. RESULTS: During the period of 2010-2011, a total of 56 HIV-infected patients and 57 healthy persons participated in this study. Among HIV positive patients, one person had positive test for HTILV-I/II representing the relative frequency of 1.8%, and in healthy individuals none of them were positive. CONCLUSION: In our survey, relative frequency of HTLV-I/II was 1.8% in HIV+ patients. This study reveals that relative frequency of HTLV-I/II in HIV positive patients is considerable but determining the need for screening of HTLV-I/II requires further investigation.

Whether vitamin D3 is effective in reducing proteinuria in type 2 diabetic patients?

BACKGROUND: Nowadays Vitamin D deficiency is a notable medical condition world-wide and also in Iran. Since, vitamin D can have renoprotective effect by inhibiting the renin-angiotensin system; it appears that low vitamin D level can worsen the renal injury in diabetic patients. This study demonstrates the effect of vitamin D3 therapy on reducing proteinuria in diabetic patients with concomitant diabetic nephropathy and vitamin D deficiency after controlling hypertension and use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type receptor blockers (ARBs). MATERIALS AND METHODS: In this randomized double blinded parallel groups clinical trial, 51 diabetic patients with proven nephropathy and vitamin D deficiency/insufficiency and stable hypertension, dyslipidemia, and hyperglycemic treatment were enrolled. The patients were divided randomly into two groups (treatment and placebo group). Patients received oral vitamin D3 (pearl 50000 IU) or placebo one pearl every week for 12 weeks. Patients were assessed at baseline and 12 weeks after intervention from the point of 25(OH) D level, and urine albumin/creatinine ration (UACR). RESULTS: Mean serum 25(OH) D concentrations were 14.06 ng/ml and 16.05 ng/ml before treatment. Furthermore, after intervention, its levels were risen to 71.23 and 17.63 in drug and placebo groups, respectively. Whereas, UACR as the main variable did not change significantly after intervention in both groups (P = 0.919). CONCLUSION: According to our finding, there was not a decrease in proteinuria in diabetic patients who received vitamin D for a period of 3 months.