XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

BACKGROUND
Red blood cell distribution width (RDW), a component of an electronic complete blood count, is a measure of heterogeneity in the size of circulating erythrocytes. In patients with symptomatic cardiovascular disease (CVD), RDW is associated with mortality. However, it has not been demonstrated that RDW is a predictor of mortality independent of nutritional deficiencies or in the general population.


METHODS
Red blood cell distribution width was measured in a national sample of 8175 community-dwelling adults 45 years or older who participated in the 1988-1994 National Health and Nutrition Examination Survey; mortality follow-up occurred through December 31, 2000. Deaths from all causes, CVD, cancer, and other causes were examined as a function of RDW.


RESULTS
Higher RDW values were strongly associated with an increased risk of death. Compared with the lowest quintile of RDW, the following were adjusted hazard ratios (HRs) for all-cause mortality (and 95% confidence intervals [CIs]): second quintile, HR, 1.1 (95% CI, 0.9-1.3); third quintile, HR, 1.2 (95% CI, 1.0-1.4); fourth quintile, HR, 1.4 (95% CI, 1.2-1.8); and fifth quintile, HR, 2.1 (95% CI, 1.7-2.6). For every 1% increment in RDW, all-cause mortality risk increased by 22% (HR, 1.22; 95% CI, 1.15-1.30; P < .001). Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B(12) deficiency, RDW remained strongly associated with mortality. The prognostic effect of RDW was observed in both middle-aged and older adults for multiple causes of death.


CONCLUSION
Red blood cell distribution width is a widely available test that is a strong predictor of mortality in the general population of adults 45 years or older.

Red Blood Cell Distribution Width and the Risk of Death in Middle-aged and Older Adults.

Type 2 diabetic kidney disease (DKD) is the most common cause of CKD and ESRD worldwide, and carries with it enormous human and societal costs. The goal of this review is to provide an update on the diagnosis and management of DKD based on a comprehensive review of the medical literature. Topics addressed include the evolving presentation of DKD, clinical differentiation of DKD from non-DKD, a state-of-the-art evaluation of current treatment strategies, and promising emerging treatments. It is expected that the review will help clinicians to diagnose and manage patients with DKD.

Diagnosis and Management of Type 2 Diabetic Kidney Disease

Loss of normal kidney function affects more than 10% of the population and contributes to morbidity and mortality. Kidney diseases are currently treated with immunosuppressive agents, antihypertensives and diuretics with partial but limited success. Most kidney disease is characterized by breakdown of the glomerular filtration barrier (GFB). Specialized podocyte cells maintain the GFB, and structure-function experiments and studies of intercellular communication between the podocytes and other GFB cells, combined with advances from genetics and genomics, have laid the groundwork for a new generation of therapies that directly intervene at the GFB. These include inhibitors of apolipoprotein L1 (APOL1), short transient receptor potential channels (TRPCs), soluble fms-like tyrosine kinase 1 (sFLT1; also known as soluble vascular endothelial growth factor receptor 1), roundabout homologue 2 (ROBO2), endothelin receptor A, soluble urokinase plasminogen activator surface receptor (suPAR) and substrate intermediates for coenzyme Q10 (CoQ10). These molecular targets converge on two key components of GFB biology: mitochondrial function and the actin-myosin contractile machinery. This Review discusses therapies and developments focused on maintaining GFB integrity, and the emerging questions in this evolving field.

The glomerular filtration barrier: a structural target for novel kidney therapies

Objective Although hypoalbuminemia is frequently found in most patients with diabetic nephropathy (DN), its relationship to the severity and progression of DN remains largely unknown. Our aim was to investigate the association between the serum albumin levels and clinicopathological features and renal outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DN. Materials and Methods A total of 188 patients with T2DM and biopsy-proven DN followed up for at least one year were enrolled. The patients were divided into four groups based on the albumin levels: normal group: ≥35 g/L (n = 87); mild group: 30-35 g/L (n = 34); moderate group: 25-30 g/L (n = 36); and severe group: <25 g/L (n = 31). The renal outcome was defined by progression to end-stage renal disease. The impact of the serum albumin level on renal survival was estimated using Cox regression analysis. Results Among the cases, the serum albumin level had a significant correlation with proteinuria, renal function, and glomerular lesions. A multivariate Cox regression analysis indicated that the severity of hypoalbuminemia remained significantly associated with an adverse renal outcome, independent of clinical and histopathological features. In reference to the normal group, the risk of progression to ESRD increased such that the hazard ratio (HR) for the mild group was 2.09 (95% CI, 0.67-6.56, p = 0.205), 6.20 (95% CI, 1.95-19.76, p = 0.002) for the moderate group, and 7.37 (95% CI, 1.24-43.83, p = 0.028) for the severe group. Conclusions These findings suggested that hypoalbuminemia was associated with a poorer renal prognosis in patients with T2DM and DN.

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The Level of Serum Albumin Is Associated with Renal Prognosis in Patients with Diabetic Nephropathy.

To determine the prevalence of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM), and the important clinical predictors of renal outcome and clinical course. We conducted a retrospective analysis of clinical, laboratory, and histopathologic data from T2DM patients with renal involvement confirmed by renal biopsy (n = 505). The outcome was defined as the progression to end-stage renal disease (ESRD). Renal biopsy revealed that 302 patients (59.8%) had DN, 174 (34.5%) had NDRD, and 29 (5.7%) had NDRD superimposed on DN. In multivariate analysis, the absence of diabetic retinopathy (DR) (odds ratio (OR) 4.171, 95% confidence interval (CI) 1.810–9.612; P = 0.001), absence of hypertension (OR 2.412, 95% CI 1.095–5.315; P = 0.029), shorter duration of diabetes (OR 1.015, 95% CI 1.008–1.022; P < 0.001), lower-risk chronic kidney disease (CKD) heat map category (green, yellow and orange) (OR 3.885, 95% CI 1.289–11.707; P = 0.016) and lower glycated hemoglobin (HbA1c) (OR 1.339, 95% CI 1.114–1.610; P = 0.002) were significant clinical predictors of NDRD. Patients with DN had a poorer 5-year renal outcome than those with NDRD, and multivariate analysis identified DN as an independent risk factor for progression to ESRD, when adjusted for important clinical variables (P < 0.05). This study has identified the absence of DR and hypertension, lower-risk CKD heat map category, shorter duration of diabetes, and lower HbA1c as useful clinical predictors of NDRD. Renal biopsy is recommended for patients with T2DM and renal disease to obtain an accurate diagnosis and determine timely disease-specific treatment, which should increase the chance of a good renal outcome.

Identification of clinical predictors of diabetic nephropathy and non-diabetic renal disease in Chinese patients with type 2 diabetes, with reference to disease course and outcome.

Background and objectives Despite advances in identifying genetic factors of diabetic kidney disease (DKD), much of the heritability remains unexplained. Nine maturity-onset diabetes in young (MODY) probands with kidney biopsy-proven DKD were selected and included in this study. The probands had more severe DKD compared with their parents with MODY, with overt proteinuria or rapid progression to ESKD. We aimed to explore the contribution of the variants in susceptibility genes of DKD to the severity of kidney phenotype between the probands and their parents. Design, setting, participants, & measurements Whole-exome sequencing was performed to identify suspected MODY probands and their families. Known DKD susceptibility genes were reviewed. Variants reported to be associated with DKD, or those with minor allele frequency Results HNF1B-MODY, CEL-MODY, PAX4-MODY, and WFS1-MODY were diagnosed among nine families. We identified 196 selected variants of 25 DKD susceptibility genes among the participants. Analysis of phenotype between probands and parents, gene function, and protein–protein interaction networks revealed that COL4A3 variants were involved in the progression of DKD. Weak granular staining of COL4α3 was observed in the glomerular basement membrane of patients with the R408H and M1209I variants, whereas strong consecutive staining was observed in patients without these variants. Moreover, more number of DKD variants were identified in probands than in their parents with MODY. Conclusions The genetic effect of more pathogenic variants in various DKD susceptibility genes, especially variants in the COL4A3 gene, partially explained the more severe kidney phenotype in probands with kidney biopsy-proven DKD.

COL4A3 Gene Variants and Diabetic Kidney Disease in MODY

Background: Red cell distribution width (RDW) has been reported to be involved in metabolic syndrome and cardiovascular events. Patients with diabetic nephropathy (DN) are often found to be with hi...

Tingli Wang

Papers

The Level of Serum Albumin Is Associated with Renal Prognosis in Patients with Diabetic Nephropathy.

Identification of clinical predictors of diabetic nephropathy and non-diabetic renal disease in Chinese patients with type 2 diabetes, with reference to disease course and outcome.

COL4A3 Gene Variants and Diabetic Kidney Disease in MODY

The association between the red cell distribution width and diabetic nephropathy in patients with type-2 diabetes mellitus.

Serum fibrinogen predicts diabetic ESRD in patients with type 2 diabetes mellitus