“…Hypovolemia and dehydration may expose frail individuals to orthostatic hypotension or postural dizziness; it is therefore important to note that SGLT2 inhibitors do not induce a significant increase in sympathetic nerve activity in response to osmotic diuresis [ 149 ]. Hypotension and dehydration could potentially decrease renal filtration, leading to acute kidney failure that may be exacerbated by recurrent and/or unresolved kidney injury [ 150 ].…”
Section: Safety Of Sglt2 Inhibitors In T2d and Renal Impairmentmentioning
Approximately half of all patients with type 2 diabetes (T2D) develop a certain degree of renal impairment. In many of them, chronic kidney disease (CKD) progresses over time, eventually leading to end-stage kidney disease (ESKD) requiring dialysis and conveying a substantially increased risk of cardiovascular morbidity and mortality. Even with widespread use of renin–angiotensin system blockers and tight glycemic control, a substantial residual risk of nephropathy progression remains. Recent cardiovascular outcomes trials investigating sodium–glucose cotransporter 2 (SGLT2) inhibitors have suggested that these therapies have renoprotective effects distinct from their glucose-lowering action, including the potential to reduce the rates of ESKD and acute kidney injury. Although patients in most cardiovascular outcomes trials had higher prevalence of existing cardiovascular disease compared with those normally seen in clinical practice, the proportion of patients with renal impairment was similar to that observed in a real-world context. Patient cardiovascular risk profiles did not relevantly impact the renoprotective benefits observed in these studies. Benefits were observed in patients across a spectrum of renal risk, but were evident also in those without renal damage, suggesting a role for SGLT2 inhibition in the prevention of CKD in people with T2D. In addition, recent studies such as CREDENCE and DAPA-CKD offer a greater insight into the renoprotective effects of SGLT2 inhibitors in patients with moderate-to-severe CKD. This review outlines the evidence that SGLT2 inhibitors may prevent the development of CKD and prevent and delay the worsening of CKD in people with T2D at different levels of renal risk.
“…Hypovolemia and dehydration may expose frail individuals to orthostatic hypotension or postural dizziness; it is therefore important to note that SGLT2 inhibitors do not induce a significant increase in sympathetic nerve activity in response to osmotic diuresis [ 149 ]. Hypotension and dehydration could potentially decrease renal filtration, leading to acute kidney failure that may be exacerbated by recurrent and/or unresolved kidney injury [ 150 ].…”
Section: Safety Of Sglt2 Inhibitors In T2d and Renal Impairmentmentioning
Approximately half of all patients with type 2 diabetes (T2D) develop a certain degree of renal impairment. In many of them, chronic kidney disease (CKD) progresses over time, eventually leading to end-stage kidney disease (ESKD) requiring dialysis and conveying a substantially increased risk of cardiovascular morbidity and mortality. Even with widespread use of renin–angiotensin system blockers and tight glycemic control, a substantial residual risk of nephropathy progression remains. Recent cardiovascular outcomes trials investigating sodium–glucose cotransporter 2 (SGLT2) inhibitors have suggested that these therapies have renoprotective effects distinct from their glucose-lowering action, including the potential to reduce the rates of ESKD and acute kidney injury. Although patients in most cardiovascular outcomes trials had higher prevalence of existing cardiovascular disease compared with those normally seen in clinical practice, the proportion of patients with renal impairment was similar to that observed in a real-world context. Patient cardiovascular risk profiles did not relevantly impact the renoprotective benefits observed in these studies. Benefits were observed in patients across a spectrum of renal risk, but were evident also in those without renal damage, suggesting a role for SGLT2 inhibition in the prevention of CKD in people with T2D. In addition, recent studies such as CREDENCE and DAPA-CKD offer a greater insight into the renoprotective effects of SGLT2 inhibitors in patients with moderate-to-severe CKD. This review outlines the evidence that SGLT2 inhibitors may prevent the development of CKD and prevent and delay the worsening of CKD in people with T2D at different levels of renal risk.
“…Hyperglycemia in type 2 diabetes is associated with micro- and macro-complications [ 5 ] and causes autonomic nervous dysfunction. Severe autonomic failure due to sympathetic and parasympathetic dysfunction typically occurs in patients with long-standing and poorly controlled diabetes [ 6 ]. The incidence of caused by uncompensated vasoconstriction during general anaesthesia was highly reported in patients with autonomic nervous dysfunction due to diabetes [ 2 ].…”
BackgroundLittle is known about the changes in autonomic function during spinal anaesthesia in type 2 diabetic patients. The purpose of the study was to assess the influence of spinal anaesthesia on the heart rate variability in type 2 diabetic patients according to the glycated hemoglobin (HbA1c) level.MethodsSixty-six patients who were scheduled for elective orthostatic lower limb surgery were assigned to three groups (n = 22, each) according to HbA1c; controlled diabetes mellitus (HbA1c < 7 %), uncontrolled diabetes mellitus (HbA1c > 7 %) and the control group. The heart rate variability was measured 10 min before (T0), and at10 min (T1), 20 min (T2) and 30 min (T3) after spinal anaesthesia.ResultsBefore spinal anaesthesia, total, low-and high-frequency power were significantly lower in the uncontrolled diabetec group than in other group (p < 0.05). During spinal anaesthesia, total, low- and high-frequency powers were did not change in the uncontrolled diabetec group while the low-frequency power in the controlled diabetec group was significantly depressed (p < 0.05). The ratio of low-to high-frequency was comparable among the groups, while it was reduced at T1-2 than at T0 in all the groups. The blood pressures were higher in the uncontrolled diabetec group than in the other groups.ConclusionsSpinal anaesthesia had an influence on the cardiac autonomic modulation in controlled diabetec patients, but not in uncontrolled diabetec patients. There were no differences in all haemodynamic variables during an adequate level of spinal anaesthesia in controlled and uncontrolled type 2 DM.Trial registrationClinicalTrials.gov NCT02137057Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-015-0125-6) contains supplementary material, which is available to authorized users.
“…Both diabetes-exposed Wt and Hif1a + / − males had a lower heart rate at 12 weeks of age (Fig. 2 e, f), which may indicate changes in cardiovascular autonomic regulation [ 31 ]. Fig.…”
BackgroundEpidemiological studies show that maternal diabetes predisposes offspring to cardiovascular and metabolic disorders. However, the precise mechanisms for the underlying penetrance and disease predisposition remain poorly understood. We examined whether hypoxia-inducible factor 1 alpha, in combination with exposure to a diabetic intrauterine environment, influences the function and molecular structure of the adult offspring heart.Methods and resultsIn a mouse model, we demonstrated that haploinsufficient (Hif1a+/−) offspring from a diabetic pregnancy developed left ventricle dysfunction at 12 weeks of age, as manifested by decreased fractional shortening and structural remodeling of the myocardium. Transcriptional profiling by RNA-seq revealed significant transcriptome changes in the left ventricle of diabetes-exposed Hif1a+/− offspring associated with development, metabolism, apoptosis, and blood vessel physiology. In contrast, both wild type and Hif1a+/− offspring from diabetic pregnancies showed changes in immune system processes and inflammatory responses. Immunohistochemical analyses demonstrated that the combination of haploinsufficiency of Hif1a and exposure to maternal diabetes resulted in impaired macrophage infiltration, increased levels of advanced glycation end products, and changes in vascular homeostasis in the adult offspring heart.ConclusionsTogether our findings provide evidence that a global reduction in Hif1a gene dosage increases predisposition of the offspring exposed to maternal diabetes to cardiac dysfunction, and also underscore Hif1a as a critical factor in the fetal programming of adult cardiovascular disease.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0713-0) contains supplementary material, which is available to authorized users.
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