Could metformin be used in patients with diabetes and advanced chronic kidney disease?

Diabetes is an important cause of end stage renal failure worldwide. As renal impairment progresses, managing hyperglycaemia can prove increasingly challenging, as many medications are contra‐indicated in moderate to severe renal impairment. Whilst evidence for tight glycaemic control reducing progression to renal failure in patients with established renal disease is limited, poor glycaemic control is not desirable, and is likely to lead to progressive complications. Metformin is a first‐line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients. Cessation of metformin in patients with progressive renal disease may not only lead to deterioration in glucose control, but also to loss of protection from cardiovascular disease in a cohort of patients at particularly high risk. We advocate the need for further study to determine the role of metformin in patients with severe renal disease (chronic kidney disease stage 4‐5), as well as patients on dialysis, or pre‐/peri‐renal transplantation. We explore possible roles of metformin in these circumstances, and suggest potential key areas for further study.     

Anaemia, diabetes and chronic kidney disease: where are we now?

Anaemia is a common finding in people with diabetes and chronic kidney disease and failure of the kidney to produce erythro-poietin in response to a falling haemoglobin concentration is a key component, correlating with the degree of albuminuria, renal dysfunction and iron deficiency. Anaemia in diabetes is associated with a number of adverse outcomes, including increased risk of all cause and cardiovascular mortality. Whether or not anaemia is a marker or mediator of adverse outcome still remains to be completely resolved. Treatment of anaemia in diabetes has quality of life benefits and reduces transfusion requirements. Correction of anaemia to normal haemoglobin concentrations is associated with significant adverse cardiovascular outcomes and is not recommended, escalating doses of erythropoiesis-stimulating agents should be avoided. The treatment of anaemia in people with diabetes and chronic kidney disease should begin with optimisation of iron stores. An aspirational haemoglobin concentration range of 10-12 g/dl with anaemia management, balances proven benefits of anaemia treatment with potential cardiovascular risk.     

Cardiometabolic syndrome and chronic kidney disease: what is the link?

The term metabolic syndrome or cardiometabolic syndrome describes the clustering of several cardiovascular and renal risk factors, including type 2 diabetes mellitus, central obesity, hypertension, and dyslipidemia. Over the past 15 years, several studies have examined the association between the metabolic/cardiometabolic syndrome or its central component, insulin resistance, with the presence of elevated urine albumin excretion. Intrarenal changes associated with the cardiometabolic syndrome result in elevated glomerular filtration rate, impaired pressure natriuresis, endothelial dysfunction related to changes in nitric oxide and, hence, impaired renal autoregulation and enhanced chronic inflammation. The aforementioned changes that occur in the cardiometabolic syndrome all contribute to the development of renal injury. While this review focuses on the epidemiology and mechanisms associated with vascular/renal injury, it must be remembered that prevention and treatment of kidney disease require a multifactorial approach. Weight loss through diet and exercise can reverse many of these pathophysiologic adaptations. Pharmacologic intervention should be aimed at achieving guideline goals and include insulin sensitizers to aid in tight glycemic control, lipid control, blockade of the renin-angiotensin-aldosterone system for blood pressure reduction, and anti-inflammatory therapies.     

Risk of chronic kidney disease in patients with non-alcoholic fatty liver disease: is there a link?

Non-alcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. Increasing recognition of the importance of NAFLD and its association with the features of the metabolic syndrome has stimulated an interest in its putative role in the development and progression of chronic kidney disease (CKD). Accumulating evidence suggests that NAFLD and CKD share many important cardio-metabolic risk factors and common pathogenetic mechanisms and that NAFLD is associated with an increased prevalence and incidence of CKD. This association appears to be independent of obesity, hypertension, and other potentially confounding factors, and it occurs both in patients without diabetes and in those with diabetes. Although further research is needed to establish a definitive conclusion, these observations raise the possibility that NAFLD is not only a marker of CKD but also might play a part in the pathogenesis of CKD, possibly through the systemic release of several pro-inflammatory/pro-coagulant mediators from the steatotic/inflamed liver or through the contribution of NAFLD itself to insulin resistance and atherogenic dyslipidemia. However, given the heterogeneity and small number of observational longitudinal studies, further research is urgently required to corroborate the prognostic significance of NAFLD for the incidence of CKD, and to further elucidate the complex and intertwined mechanisms that link NAFLD and CKD. If confirmed in future large-scale prospective studies, the potential adverse impact of NAFLD on kidney disease progression will deserve particular attention, especially with respect to the implications for screening and surveillance strategies in the growing number of patients with NAFLD.     

Is food insufficiency associated with health status and health care utilization among adults with diabetes?

OBJECTIVES: Preliminary studies have shown that among adults with diabetes, food insufficiency has adverse health consequences, including hypoglycemic episodes and increased need for health care services. The purpose of this study was to determine the prevalence of food insufficiency and to describe the association of food insufficiency with health status and health care utilization in a national sample of adults with diabetes. METHODS: We analyzed data from adults with diabetes ( n =1,503) interviewed in the Third National Health and Nutrition Examination Survey. Bivariate and multivariate analyses were used to examine the relationship of food insufficiency to self-reported health status and health care utilization. RESULTS: Six percent of adults with diabetes reported food insufficiency, representing more than 568,600 persons nationally (95% confidence interval, 368,400 to 768,800). Food insufficiency was more common among those with incomes below the federal poverty level (17% vs 4%, P < or = .001). Adults with diabetes who were food insufficient were more likely to report fair or poor health status than those who were not (63% vs 43%; odds ratio, 2.2; P=.05). In a multivariate analysis, fair or poor health status was independently associated with poverty, nonwhite race, low educational achievement, and number of chronic diseases, but not with food insufficiency. Diabetic adults who were food insufficient reported more physician encounters, either in clinic or by phone, than those who were food secure (12 vs 7, P<.05). In a multivariate linear regression, food insufficiency remained independently associated with increased physician utilization among adults with diabetes. There was no association between food insufficiency and hospitalization in bivariate analysis. CONCLUSIONS: Food insufficiency is relatively common among low-income adults with diabetes and was associated with higher physician utilization.     

Leaky gut and diabetes mellitus: what is the link?

Diabetes mellitus is a chronic disease requiring lifelong medical attention. With hundreds of millions suffering worldwide, and a rapidly rising incidence, diabetes mellitus poses a great burden on healthcare systems. Recent studies investigating the underlying mechanisms involved in disease development in diabetes point to the role of the dys‐regulation of the intestinal barrier. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of infectious agents and dietary antigens to mucosal immune elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Understanding the factors regulating the intestinal barrier function will provide important insight into the interactions between luminal antigens and immune response elements. This review analyses recent advances in the mechanistic understanding of the role of the intestinal epithelial barrier function in the development of type 1 and type 2 diabetes. Given our current knowledge, we may assume that reinforcing the intestinal barrier can offer and open new therapeutic horizons in the treatment of type 1 and type 2 diabetes.     

Valvular and perivalvular involvement in patients with chronic kidney disease

Mitral annular calcification (MAC) and aortic valve calcification (AVC) are the most common valvular and perivalvular abnormalities in patients with chronic kidney disease (CKD). Both MAC and AVC occur at a younger age in CKD patients than in the general population. AVC progresses to aortic stenosis and mild aortic stenosis progresses to severe aortic stenosis at a more rapid rate in patients with CKD than in the general population. The use of calcium-free phosphate binders in such patients may reduce the calcium burden in valvular and perivalvular structures and retard the rate of progression of aortic stenosis. Despite high rates of morbidity and mortality, the prognosis associated with valve surgery in patients with CKD is better than without valve surgery. Infective endocarditis remains an important complication of CKD, particularly in those treated with hemodialysis.     

Patients with chronic hepatitis C receiving treatment with direct acting antivirals: How is this population changing?

Background and aimsDirect acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing.Materials and methodsWe retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment.ResultsIn the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p<0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p<0.001). Instead, the yearly number of experienced patients decreased significantly (p<0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p<0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P<0.05).ConclusionsThe population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.     

Dietary fats and diabetes mellitus: is there a good fat?

As knowledge of the fatty acid functions has increased, so has the complexity of making dietary fat recommendations to people with type 2 diabetes. Oleic acid seems to offer a slight advantage over linoleic acid in reducing plasma glucose, insulin levels, total cholesterol, low-density lipoproteins (LDL_s), and triglycerides, but may also have atherogenic properties through another mechanism. A diet containing a higher proportion of polyunsaturated fatty acids (PUFA_s) may require a concomitant increase in antioxidant intake because PUFA_s oxidize easily and are then converted to oxidized LDL, which is more atherogenic. In addition to raising total and LDL cholesterol, long chain saturated free fatty acids may interact with plasma glucose to increase insulin secretion. Omega-3 fatty acids decrease triglycerides and reduce the risk of fatal cardiac arrhythmias. Glycemic control does not appear to be adversely affected by omega-3 fatty acids at amounts of up to 3 g/d.     

Type 2 diabetes mellitus and osteopenia: is there an association?

We report the results of bone mineral density (BMD) measurements in type 2 diabetic patients, in comparison to healthy controls. In this prospective study, a total of 277 subjects (aged 30–60 years) with type 2 diabetes mellitus, outpatients at the Cukurova Medical School Hospital, were evaluated for BMD at L₁–L₄ lumbar vertebrae and at the femur (neck, trochanter, Ward's triangle and total) by DEXA (dual energy X-ray absorptiometry). The patients' diabetes duration, treatment, glycemic control and chronic diabetic complications were recorded, and these data were evaluated for any relationship in respect to the BMD measurements. BMD results of the diabetic patients were compared with those of 262 healthy non-diabetic control subjects living in the same geographic region. BMD was found to be increased at the femoral neck among diabetic women and men aged 51–60 years. However, BMD values at lumbar regions of diabetic men where lower than control in all age group. There was no difference in values of BMD for both genders in the other regions. Type 2 diabetic patients may have lower, similar or higher BMD measurements at different ages and anatomic regions, so each patient should be evaluated individually. Further studies are needed to make a conclusion on this issue. Received: 18 October 2002 / Accepted in revised form: 2 April 2003 Correspondence to M. Sert     

Obesity--the risk factor of cardiovascular disease in patients with chronic kidney disease?

In general population obesity is regarded as a predisposing factor for chronic disease such as type 2 diabetes and cardiovascular disease. Obesity increases the risk of kidney disease and adversely affects the progress of kidney disease among patients with diagnosed kidney disease. The main reason of mortality in chronic kidney disease patients is cardiovascular disease, however, the real meaning of obesity as a risk factor of cardiovascular diseases is still uncertain. While in a general population obesity causes higher cardiovascular mortality, many studies reflect inverse association in chronic kidney disease patients. Obesity is associated with better survival, contrary to general population obesity appears to be a protective factor of cardiovascular disease. The name of this phenomenon is "reverse epidemiology" or "obesity paradox", in dialysis patients known as a "risk-factor-paradox". Some studies do not confirm this paradox association in patients with chronic kidney disease.     

Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?

Chronic kidney disease (CKD) is strongly associated with cardiovascular disease (CVD); a graded inverse relationship between estimated glomerular filtration rate (eGFR) and cardiovascular event rates has emerged from large-scale observational studies. Chronic kidney disease is also associated with endothelial dysfunction (ED) although the precise relationship with GFR and the "threshold" at which ED begins are contentious. Abnormal endothelial function is certainly present in late-stage CKD but data in early-stage CKD appear confounded by disease states such as diabetes and hypertension which themselves promote ED. Thus, the direct effect of a reduction in GFR on endothelial function and, therefore, cardiovascular (CV) risk is far from completely established. In human studies, the precise duration of kidney impairment is seldom known and the onset of CVD often insidious, making it difficult to determine exactly when CVD first appears in the context of CKD. Kidney donors provide a near-ideal experimental model of CKD; subjects undergo an acute change from normal to modestly impaired renal function at the time of nephrectomy and lack the confounding co-morbidity that has made observational studies of CKD patients so challenging to interpret. By examining changes in endothelial function in living kidney donors before and after nephrectomy, useful insight might be gained into the pathophysiology of CVD in CKD and help determine whether targeting ED or the renal disease itself has the potential to reduce CV risk.     

Risk of cardiovascular disease and chronic kidney disease in diabetic patients with non-alcoholic fatty liver disease: just a coincidence?

Non-alcoholic fatty liver disease (NAFLD) is estimated to afflict ~20-30% of the general population, and over 70% of the patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and diabetes, NAFLD will be, if not already there, an epidemic. The consequences of NAFLD are numerous, and range from progression to chronic liver disease with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, to being a contributor to both cardiovascular disease (CVD) and chronic kidney disease (CKD). NAFLD is, therefore, a complex problem with implications far beyond the liver. This review focuses on the rapidly expanding body of clinical evidence suggesting that NAFLD is associated with an increased prevalence and incidence of both CVD and CKD in patients with diabetes. This association appears to be independent of obesity, hypertension, and other potential confounding factors. However, given the heterogeneity and small number of observational studies, further research is urgently required to corroborate the prognostic role of NAFLD in the development and progression of CVD and CKD among patients with diabetes, and to further elucidate the complex and intertwined mechanisms that link NAFLD with these adverse outcomes.     

Can we prolong life of patients with advanced chronic kidney disease: what is the clinical evidence?

The risk of death in patients with advanced chronic kidney disease (CKD) is markedly higher than in the population without CKD, even in patients suffering from advanced cardiovascular disease. Among several clinical features of CKD, the following are considered the most important areas of therapeutic intervention: hypertension, lipid abnormalities, mineral and bone disorders of CKD (previously known as renal osteodystrophy), renal anemia, and uremic toxicity. However, numerous treatment strategies, which are applied based on the understanding of underlying pathologies, did not result in significantly improved prognosis. These strategies include lowering of blood pressure, use of statins, control of hyperphosphatemia and hyperparathyroidism, erythropoesis-stimulating agents, use of better and more biocompatible dialysis membranes, and higher dialysis dose. In this critical review, we discuss the most important, large clinical trials, in which the above therapies failed to show desirable results and to reduce mortality in patients with advanced CKD.