High-protein diet: A barrier to the nephroprotective effects of sodium-glucose co-transporter-2 inhibitors?

Glomerular hyperfiltration is a common finding in patients with diabetes and poor glycaemic control; whole-kidney hyperfiltration, with glomerular filtration rate (GFR) values above normal, should be differentiated from single nephron hyperfiltration, consequent to nephron loss and compensatory hyperfiltration of the remnant nephrons. This is the result of an imbalance between the vascular tone of the afferent and efferent arterioles. Hormonal influences and/or an impaired tubuloglomerular feedback (TGF) system, because of excessive sodium (Na⁺) and glucose reabsorption in the proximal tubule, contribute to determine hyperfiltration. Sodium-glucose co-transporter-2 inhibitors (SGLT2is), by decreasing Na⁺ reabsorption and increasing the delivery of Na⁺ to the macula densa, lead to normalization of TGF, and, consequently, decrease GFR (both whole and single nephron). High-protein diets are popular among patients with type 1 and type 2 diabetes; importantly, 80% of the amino acids are also reabsorbed in the proximal tubule of the nephron and are transported by symporters that use the electro-chemical gradient of Na⁺. Indeed, an acute protein load is associated with increased Na⁺ reabsorption and an increase in GFR. Here, we hypothesize that high-protein diets, by increasing Na⁺ reabsorption and GFR, may offset the positive renal effects of SGLT2is.     

Cardiovascular risk factor management in patients with diabetes: Does management differ with disease duration?

AimsOur objective was to examine risk factor modification targets and treatment in relation to duration of diabetes.MethodsThe Diabetes Mellitus Status in Canada (DM-SCAN) study collected data on 5109 patients with type 2 diabetes mellitus (T2DM) in 2012 in primary care. We compared the prevalence of vascular complications, treatment targets, and interventions between patients with diagnosed diabetes duration ≤10 and > 10 years.ResultsPhysicians more frequently assigned HbA1c (glycated hemoglobin) targets of 7.1–8.5% (54–69 mmol/mol) to patients with longer duration of diabetes (n = 1647) (19.8% vs 9.5%, p < 0.001). Patients with longer duration of diabetes were less likely to achieve HbA1c targets of ≤7.0% (53 mmol/mol) (39% vs. 55%, p < 0.001), had similar likelihood of achieving blood pressure targets of ≤130/80 mmHg (38% vs. 36%, p = 0.26) and were more likely to achieve LDL-C targets of ≤2.0 mmol/L (≤77.3 mg/dL) (63% vs. 53%, p < 0.001) compared to patients with shorter duration of diabetes (n = 3462). Achievement of all three targets between both groups were similar (13% vs. 13%, p = 0.82). Overall, patients with longer duration of diabetes were more likely to be prescribed anti-hyperglycemic, anti-hypertensive, lipid-lowering medications and referred for diabetes education.ConclusionsOnly 13% of patients achieved glycemic, blood pressure, and LDL-C targets irrespective of duration of diabetes. Despite being managed with more medications, patients with longer duration of diabetes were less likely to achieve glycemic targets. More focus is needed on developing methods to bridge best care and real-world practice.     

Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent “toxic” effect on pancreatic islets resulting in β‐cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A_1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.     

Cardiovascular risk factors in patients with type 2 diabetes. Do we follow the guidelines?

OBJECTIVE: To assess the degree of control of modifiable cardiovascular risk factors (CRFs) in type 2 diabetic patients. STUDY DESIGN AND METHODS: Cross-sectional study in 501 patients with type 2 diabetes mellitus. The following parameters were used to define optimal control: glycated haemoglobin (HbA(1C)) <7.0%, fasting plasma glucose (FPG) <7.2 mmol/l, postprandial capillary glucose (PCG) <10.0 mmol/l, high-density lipoprotein cholesterol (HDL-C) >1.1 mmol/l, low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/l, triglyceride levels (TG) <1.7 mmol/l, systolic blood pressure (SBP) <130 mmHg, diastolic blood pressure (DBP) <80 mmHg, body mass index (BMI) <25 kg/m2, waist circumference (WC) <88 cm in women and <102 cm in men, and current non-smoking status. The use of various cardioprotective medications was also evaluated. RESULTS: Mean (+/-S.D.) age was 65.4 +/- 11.9 years, 218 (44%) were male. Ninety-six (19%) met coronary artery disease (CAD). Two hundred seven patients (41%) had an HbA(1C) <7.0%, 134 (27%) a FPG <7.2 mmol/l and 231 of 353 (65%) a PCG <10.0 mmol/l. Only 206 (41%) achieved an LDL-C <2.6 mmol/l, but 370 (74%) and 308 (62%) reached an HDL-C >1.1 mmol/l and a TG levels <1.7 mmol/l, respectively. In 359 (72%) patients DBP was <80 mmHg, but in only 136 (27%) was SBP <130 mmHg. Sixty four (13%) achieved a BMI <25 kg/m2, and 420 (84%) were non-smokers. Forty three (15%) women and 104 (48%) men had a WC <88 or <102 cm, respectively. None of the patients had optimal control of all CRFs. CONCLUSIONS: These data demonstrate poor control of modifiable CRFs in the population studied, and support the need for great effort to achieve the recommended goals.     

Optimizing target-organ protection in patients with diabetes mellitus: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers?

High blood pressure in the setting of type 1 and type 2 diabetes is commonly associated with the earlier development of target-organ damage, including cardiovascular and cerebrovascular disease and progressive renal insufficiency. The major goal of treating high blood pressure in this population is to prevent or reduce the likelihood of targetorgan damage. The treatment goal for high blood pressure, therefore, has to be defined based on optimal means of preventing cardiovascular and renal events. The reduction of high blood pressure with pharmacologic therapy is associated with reduction of cardiovascular events, renal disease, and associated mortality. However, many questions remain. Some of the basic and important questions include the following: What should be the goal of treated blood pressure in the diabetic, and are there preferred agents that should be used in the hypertensive diabetic population? How do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers fit in? Are there advantages of one class over the other? The goal of this review is to summarize the recent clinical trial findings and try to provide recommendations based on the evidence of these trials to help the clinician better choose blood pressure goals and treatment strategies in the diabetic population.     

Why is blood pressure so hard to control in patients with type 2 diabetes?

Resistance to antihypertensive drugs is common in hypertensive patients with type 2 diabetes. This is unfortunate because hypertension is one of the most important risk factors for development of cardiovascular events, and the goal blood pressure level is set lower in diabetic subjects than in nondiabetic subjects. Previous outcome trials in diabetic subjects have mainly focused on end points such as microalbuminuria or the incidence of cardiovascular events rather than on reduction of blood pressure; some reports, however, have suggested mechanisms for the drug resistance. These include several clinical conditions known to be associated with difficulty in reducing blood pressure specifically in diabetes mellitus: change in the renin-angiotensin system and chymase, volume overload, central sympathetic hyperactivity, sleep apnea, secondary hypertension, pseudoresistance (white coat hypertension), and poor compliance related to subclinical depression. In this review, the authors focus on the mechanisms of resistance to antihypertensive therapy (particularly for monotherapy with either angiotensin-converting enzyme inhibitors or angiotensin II antagonists) in the treatment of diabetic hypertension.     

Uncontrolled hypertension in patients with type 2 diabetes: What are the correlates?

Suboptimal blood pressure (BP) control in patients with type 2 diabetes is associated with adverse micro‐ and macrovascular complications. This study aimed to investigate the predictors of uncontrolled hypertension in an Iranian population with type 2 diabetes. This is a cross‐sectional study of 2612 patients with type 2 diabetes, including 944 patients with hypertension. Controlled and uncontrolled hypertension were assessed. Multivariate logistic regression modeling was used to determined independent predictors of uncontrolled hypertension. Of 2612 patients with type 2 diabetes, 944 (36.1%) patients had hypertension. Of all patients with hypertension, 580 (61.4%) were still on monotherapy. Uncontrolled hypertension was detected in 536 participants (56.8%). Patients with uncontrolled hypertension had significantly higher body mass index (BMI) (29.8±4.8 vs. 28.6±4.6), waist circumference (99.11±10.95 vs. 96.68±10.92), pulse pressure (67.3±17.3 vs. 48.4±10.7), total cholesterol (177.1±45.5 vs. 164.3±40.5), non‐HDL cholesterol (133.0±43.5 vs. 120.1±38.7), triglycerides (175.7±80.3 vs. 157.4±76.7), and Atherogenic Index of Plasma (AIP) (0.57±0.23 vs. 0.52±0.24) (p < .05 for all of them) compared to patients with controlled hypertension. Multivariate logistic regression analysis revealed that uncontrolled hypertension was significantly associated with BMI (p = .001), pulse pressure (p = .001), total cholesterol (p = .006), and non‐HDL cholesterol (p = .009). In patients with triglycerides levels > 200 mg/dl non‐HDL cholesterol had a significant correlation with uncontrolled hypertension (OR = 4.635, CI95%:1.781–12.064, p = .002). In conclusion, BMI, pulse pressure, total cholesterol, and non‐HDL cholesterol are significant predictors of uncontrolled hypertension in patients with type 2 diabetes. Also, ineffective monotherapy, medical inertia and patients’ non‐compliance were other contributors to the uncontrolled hypertension.     

Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin?

Premature coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In certain age groups, the risk can be >50 times that of an age-matched population. This population also has an increased prevalence of several key classic risk factors that contribute to the CHD development. Chronic inflammation, anti-phospholipid antibodies and exposure to steroid therapy are also likely to have an impact. We have adopted a proactive approach to classic risk factor management with 'ideal targets' based on viewing SLE as a CHD equivalent condition. In this context, a significant proportion of SLE patients (approximately 30%) will require statins and the majority would be treated with aspirin prophylaxis. Better control of the underlying inflammatory disease is also likely to play an important role and the relative safety of anti-malarials allows their consideration as an adjunct in a large proportion of patients. Well-conducted clinical trials are now needed to advance beyond these initial recommendations.