This document discusses various treatment strategies for diabetic nephropathy, including ACE inhibitors, ARBs, glycemic control, SGLT2 inhibitors, and GLP-1 receptor agonists. It provides evidence from clinical trials that ACE inhibitors and ARBs reduce kidney disease progression in both type 1 and type 2 diabetes. Intensive glycemic control with medications or pancreas transplant can slow kidney disease, though the evidence is less clear for type 2 diabetes. Newer drugs like SGLT2 inhibitors and GLP-1 agonists may provide renoprotection based on trial results showing reduced albuminuria, kidney function decline, and cardiovascular outcomes.
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
Diabetic neuropathy is a serious and common complication of type 1 and type 2 diabetes.
Ocurres over 90% of diabetes people.
Presence of symptoms and or signs of nerve dysfunction in people with diabetes after all other causes have been excluded.
It’s a type of nerve damage caused by long-term high blood sugar levels.
The condition usually develops slowly, sometimes over the course of several decades.
Distal Symmetrical Neuropathy(DSN) most common form of DN.
DSN affects the toes and distal foot, but slowly progresses proximally to involve the feet and legs in a stocking distribution.
It is also characterized by a progressive loss of nerve fibers affecting both the autonomic and somatic divisions, thereby diabetic retinopathy and nephropathy can occur.
Foot ulceration and painful neuropathy are the main clinical consequences of DSPN, linked with higher morbidity and mortality
Recent advancement in managing diabetic nephropathypp_shivgunde
This document discusses recent advances in managing and understanding diabetic nephropathy. It begins with an introduction to diabetes and chronic kidney disease prevalence and prognosis. It then covers the pathophysiology of diabetic nephropathy and the current standard tripartite approach of intensive blood glucose control, blood pressure control, and RAAS blockade. Novel therapeutic modalities such as exploiting the renin-angiotensin-aldosterone axis through dual or combined blockade and aldosterone antagonism are also discussed.
Diabetic nephropathy has become a leading cause of end-stage renal failure. Approximately 40% of patients with diabetes develop nephropathy, which is characterized by persistent albuminuria, elevated blood pressure, and decline in kidney function. Good glycemic and blood pressure control can delay the onset and slow the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are effective in treating diabetic nephropathy through their blood pressure lowering effects and additional renal protection. Intensive management of all cardiovascular risk factors can further slow the progression of kidney damage in patients with diabetes.
Empagliflozin is an SGLT2 inhibitor that has shown cardiovascular benefits in clinical trials. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, leading to increased glucose excretion and reduced blood glucose levels. Empagliflozin in particular has demonstrated reductions in cardiovascular death and hospitalization for heart failure. However, SGLT2 inhibitors also carry risks like genitourinary infections and volume depletion that require monitoring. Overall, SGLT2 inhibitors provide an additional treatment option for type 2 diabetes that can help lower glucose levels while also reducing cardiovascular outcomes.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
The Importance of CV Outcomes in Patients T2 Diabetes Mellitus Sara Temkit
Empa-reg outcome and Leader trials have substantiated the use of Liraglutide and Empagliflozin (as add-ons to Metformin in patients at high CV risk). This has led to changes in Canadian Diabetes Association (CDA) guidelines.
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
Diabetic neuropathy is a serious and common complication of type 1 and type 2 diabetes.
Ocurres over 90% of diabetes people.
Presence of symptoms and or signs of nerve dysfunction in people with diabetes after all other causes have been excluded.
It’s a type of nerve damage caused by long-term high blood sugar levels.
The condition usually develops slowly, sometimes over the course of several decades.
Distal Symmetrical Neuropathy(DSN) most common form of DN.
DSN affects the toes and distal foot, but slowly progresses proximally to involve the feet and legs in a stocking distribution.
It is also characterized by a progressive loss of nerve fibers affecting both the autonomic and somatic divisions, thereby diabetic retinopathy and nephropathy can occur.
Foot ulceration and painful neuropathy are the main clinical consequences of DSPN, linked with higher morbidity and mortality
Recent advancement in managing diabetic nephropathypp_shivgunde
This document discusses recent advances in managing and understanding diabetic nephropathy. It begins with an introduction to diabetes and chronic kidney disease prevalence and prognosis. It then covers the pathophysiology of diabetic nephropathy and the current standard tripartite approach of intensive blood glucose control, blood pressure control, and RAAS blockade. Novel therapeutic modalities such as exploiting the renin-angiotensin-aldosterone axis through dual or combined blockade and aldosterone antagonism are also discussed.
Diabetic nephropathy has become a leading cause of end-stage renal failure. Approximately 40% of patients with diabetes develop nephropathy, which is characterized by persistent albuminuria, elevated blood pressure, and decline in kidney function. Good glycemic and blood pressure control can delay the onset and slow the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are effective in treating diabetic nephropathy through their blood pressure lowering effects and additional renal protection. Intensive management of all cardiovascular risk factors can further slow the progression of kidney damage in patients with diabetes.
Empagliflozin is an SGLT2 inhibitor that has shown cardiovascular benefits in clinical trials. SGLT2 inhibitors work by inhibiting glucose reabsorption in the kidneys, leading to increased glucose excretion and reduced blood glucose levels. Empagliflozin in particular has demonstrated reductions in cardiovascular death and hospitalization for heart failure. However, SGLT2 inhibitors also carry risks like genitourinary infections and volume depletion that require monitoring. Overall, SGLT2 inhibitors provide an additional treatment option for type 2 diabetes that can help lower glucose levels while also reducing cardiovascular outcomes.
Empagliflozin and Cardiovascular OutcomesUyen Nguyen
1) The EMPA-REG OUTCOME trial evaluated the cardiovascular outcomes of empagliflozin compared to placebo in over 7000 patients with type 2 diabetes at high risk of cardiovascular events.
2) Empagliflozin was found to significantly reduce the risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo.
3) Additional benefits observed with empagliflozin included a significant reduction in all-cause mortality, cardiovascular mortality, and hospitalization for heart failure.
The Importance of CV Outcomes in Patients T2 Diabetes Mellitus Sara Temkit
Empa-reg outcome and Leader trials have substantiated the use of Liraglutide and Empagliflozin (as add-ons to Metformin in patients at high CV risk). This has led to changes in Canadian Diabetes Association (CDA) guidelines.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Diabetic nephropathy medical managementNilesh Jadhav
1. Diabetic nephropathy is a chronic kidney disease caused by damage to the kidneys over many years as a result of diabetes. It is the most common cause of end-stage renal disease.
2. Management of diabetic nephropathy focuses on optimal control of blood glucose, blood pressure, lipids through medication, lifestyle changes, and monitoring for progression of kidney disease.
3. RAAS blockade using ACE inhibitors, ARBs, or renin inhibitors is important treatment but requires monitoring of potassium and kidney function. Referral to a nephrologist is recommended for atypical cases or rapid decline in kidney function.
1) Diabetes is now the leading cause of end-stage renal disease (ESRD) in the United States, surpassing other causes like hypertension.
2) Diabetic nephropathy follows a typical progression from increased kidney function to protein in the urine to declining kidney function over many years.
3) Tight control of blood pressure, blood sugar, and use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. Strict control of blood glucose, blood pressure, angiotensin system inhibitors, and other risk factors can help prevent or slow the progression of kidney damage. The stages include early hyperfiltration, development of microalbuminuria, progression to macroalbuminuria and renal failure. Management focuses on glycemic control, blood pressure reduction, angiotensin blockade, cholesterol control, and management of anemia and cardiovascular risk factors to preserve kidney function for as long as possible.
This document discusses the management of diabetic nephropathy. It begins with defining diabetic nephropathy as a clinical syndrome characterized by persistent albuminuria, progressive decline in glomerular filtration rate, elevated blood pressure, worse glycemic control, hypertension, and genetic predisposition. It then outlines the typical progression of diabetic kidney disease and reviews risk factors. Current treatment strategies are aimed at strict glycemic control, blood pressure control, reducing proteinuria, and preserving renal function through ACE inhibitors, ARBs, and lifestyle modifications like weight loss and smoking cessation. Newer treatments continue to be explored, but therapeutic intervention works best when begun early and glycemia, blood pressure, and proteinuria are well controlled.
Anti-Diabetics For Cardiac Patients The Proper Selectionmagdy elmasry
Cardiovascular Disease and Type 2 Diabetes.Tight glycaemic control can reduce microvascular complications of T2DM, but does not lower CV risk sufficiently.
Multifactorial intervention, comprising of lowering lipid levels and BP, and use of aspirin, has been shown to reduce vascular complications and mortality.Shifting the Paradigm in Diabetes Care
Treating Diabetes Beyond A1C :Considerations for Cardiovascular Protection.
Diabetic nephropathy is the leading cause of end-stage renal disease. About 20-30% of patients with type 1 or type 2 diabetes develop nephropathy, which involves stages of hyperfiltration, microalbuminuria, proteinuria, and finally end-stage renal disease. Risk factors include age, race, ethnicity, history of microalbuminuria, hypertension, poor glycemic control, and smoking. Treatment aims to control blood pressure and block the renin-angiotensin system using ACE inhibitors, angiotensin receptor blockers, or calcium channel blockers to slow the progression of kidney damage.
Do T2DM drugs have CV benefit for Type 1 Diabetes ?magdy elmasry
T1D Exchange , average A1C levels have not improved .How can adjunctive therapies ( added to insulin ) can help?
The Removal Trial.Three main clinical trials :
DEPICT with dapagliflozin ,
EASE with empagliflozin , and
inTANDEM with sotagliflozin.
Seminario 6 Empagliflozin, cardiovascular outcomes, and mortality in type 2 d...Mijail JN
This document summarizes a clinical trial that studied the effects of empagliflozin, an inhibitor of sodium-glucose cotransporter-2, on cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular events. A total of 7020 patients were randomly assigned to receive either 10 mg or 25 mg of empagliflozin or a placebo once daily for a median of 3.1 years. The trial found that empagliflozin reduced the primary composite outcome of cardiovascular death, non-fatal heart attack or non-fatal stroke compared to placebo, as well as reducing rates of death from any cause, death from cardiovascular causes, and hospitalization for heart failure. Genital infections were more common
This document discusses diabetic neuropathy. It begins with some global statistics on the prevalence and costs of diabetic neuropathy. It then discusses the pathology, risk factors, presentations, diagnosis and treatments of various types of diabetic neuropathy, including diffuse symmetrical sensorimotor polyneuropathy, autonomic neuropathy, and diffuse small fibre neuropathy. Tight glycemic control is emphasized as an important part of prevention and treatment.
This document discusses dysglycemia and chronic kidney disease (CKD). It begins with an agenda that covers background, pathophysiology, glycemic control, and insulin therapy and conclusions. It then discusses how diabetes is the most common cause of end-stage renal disease. It explains how dysglycemia includes sustained hyperglycemia and acute glucose fluctuations. The kidney plays an important role in glucose homeostasis by filtering, reabsorbing, and producing glucose. Both hyperglycemia and glucose variability can drive diabetic kidney disease through various pathways like protein kinase C activation and oxidative stress. Maintaining good glycemic control through lowering HbA1c can significantly reduce microvascular and cardiovascular complications in patients with CKD.
The document discusses cardiovascular risk and management in patients with diabetes, including treating cardiovascular risk factors as aggressively in diabetic patients as in non-diabetic patients with prior heart attacks, aiming for tighter glycemic control to reduce cardiovascular events and mortality, and considering individual patient factors and comorbidities when setting glycemic targets and selecting antihyperglycemic therapies, particularly in acute care settings where basal insulin regimens are preferred over sliding scales.
Dyslipidemia-latest guidlines-Review of Guidlines by Dr.Jayasoorya p gjpgkmr
Dyslipidemia newer guidelines
2019 ESC/EAS GUIDLINES FOR MANAGEMENT OF DYSLIPIDEMIA
2019 JUNE UPDATED AMERICAN COLLEGE OF CARDIOLOGY GUIDLINES FOR MANAGEMENT OF DYSLIPIDEMIA
This document provides information on antihypertensive drugs. It begins by listing the specific learning objectives, which include defining hypertension, discussing types and drugs for treatment, mechanisms of action, adverse effects, and considerations for use in various conditions. It then covers primary and secondary hypertension, urgency vs emergency, and mnemonics for drug classes. Individual drug classes are discussed in detail, including diuretics, ACE inhibitors, ARBs, calcium channel blockers, arteriolar vasodilators, and beta blockers. Mechanisms, advantages, disadvantages, and special considerations are provided for each class.
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
This document discusses different types of iatrogenic (medically induced) diabetes, including:
1) Pancreatogenic diabetes caused by pancreatic diseases or procedures that damage the pancreas.
2) Drug-induced diabetes caused by medications like corticosteroids, antipsychotics, immunosuppressants, protease inhibitors, and chemotherapy drugs.
3) Post-transplant diabetes that develops in some organ transplant recipients due to immunosuppressant drugs and other risk factors.
The document provides details on the mechanisms and risk factors for each type of iatrogenic diabetes.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
DKD is a leading cause of ESRD in the US, affecting 30-40% of those with diabetes. Poor glycemic control and hypertension are major risk factors for developing and progressing DKD. Clinical trials have shown that intensive control of blood glucose and blood pressure can delay and prevent kidney disease. New drugs targeting the kidney are showing promise in reducing albuminuria and slowing kidney function decline in DKD patients.
This document summarizes diabetic kidney disease (DKD), the leading cause of end-stage renal disease in the United States. DKD risk factors include age, sex, race, family history, hypertension, and poor glycemic control. Intensive glucose and blood pressure control can delay DKD progression. While current therapies can slow DKD, innovation is still needed to improve outcomes given residual risks. Novel drug classes targeting DKD mechanisms may provide future treatment options.
The CREDENCE trial evaluated the effect of canagliflozin vs placebo on renal outcomes in patients with type 2 diabetes and chronic kidney disease. Over 2.6 years of follow up:
1) Canagliflozin reduced the composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death by 30% compared to placebo.
2) Canagliflozin also reduced cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure by 30% compared to placebo.
3) The trial demonstrated that canagliflozin provided renoprotective and cardiovascular benefits in patients with type 2 diabetes and chronic kidney disease.
Diabetic nephropathy medical managementNilesh Jadhav
1. Diabetic nephropathy is a chronic kidney disease caused by damage to the kidneys over many years as a result of diabetes. It is the most common cause of end-stage renal disease.
2. Management of diabetic nephropathy focuses on optimal control of blood glucose, blood pressure, lipids through medication, lifestyle changes, and monitoring for progression of kidney disease.
3. RAAS blockade using ACE inhibitors, ARBs, or renin inhibitors is important treatment but requires monitoring of potassium and kidney function. Referral to a nephrologist is recommended for atypical cases or rapid decline in kidney function.
1) Diabetes is now the leading cause of end-stage renal disease (ESRD) in the United States, surpassing other causes like hypertension.
2) Diabetic nephropathy follows a typical progression from increased kidney function to protein in the urine to declining kidney function over many years.
3) Tight control of blood pressure, blood sugar, and use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy.
Cardiovascular safety of anti-diabetic drugs.Cardiovascular Outcome Trials ...magdy elmasry
Cardiologists and diabetes.Target organs and action mechanism of antidiabetic drugs.Cardiovascular Outcome Trials
( CVOTs ) in Diabetes.Completed and ongoing CVOTs in type 2 diabetes.Diabetes Medications
and
Cardiovascular Impact.Recommendations for management of diabetes
Cardiovascular safety of anti-diabetic drugs.
Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. Strict control of blood glucose, blood pressure, angiotensin system inhibitors, and other risk factors can help prevent or slow the progression of kidney damage. The stages include early hyperfiltration, development of microalbuminuria, progression to macroalbuminuria and renal failure. Management focuses on glycemic control, blood pressure reduction, angiotensin blockade, cholesterol control, and management of anemia and cardiovascular risk factors to preserve kidney function for as long as possible.
This document discusses the management of diabetic nephropathy. It begins with defining diabetic nephropathy as a clinical syndrome characterized by persistent albuminuria, progressive decline in glomerular filtration rate, elevated blood pressure, worse glycemic control, hypertension, and genetic predisposition. It then outlines the typical progression of diabetic kidney disease and reviews risk factors. Current treatment strategies are aimed at strict glycemic control, blood pressure control, reducing proteinuria, and preserving renal function through ACE inhibitors, ARBs, and lifestyle modifications like weight loss and smoking cessation. Newer treatments continue to be explored, but therapeutic intervention works best when begun early and glycemia, blood pressure, and proteinuria are well controlled.
Anti-Diabetics For Cardiac Patients The Proper Selectionmagdy elmasry
Cardiovascular Disease and Type 2 Diabetes.Tight glycaemic control can reduce microvascular complications of T2DM, but does not lower CV risk sufficiently.
Multifactorial intervention, comprising of lowering lipid levels and BP, and use of aspirin, has been shown to reduce vascular complications and mortality.Shifting the Paradigm in Diabetes Care
Treating Diabetes Beyond A1C :Considerations for Cardiovascular Protection.
Diabetic nephropathy is the leading cause of end-stage renal disease. About 20-30% of patients with type 1 or type 2 diabetes develop nephropathy, which involves stages of hyperfiltration, microalbuminuria, proteinuria, and finally end-stage renal disease. Risk factors include age, race, ethnicity, history of microalbuminuria, hypertension, poor glycemic control, and smoking. Treatment aims to control blood pressure and block the renin-angiotensin system using ACE inhibitors, angiotensin receptor blockers, or calcium channel blockers to slow the progression of kidney damage.
Do T2DM drugs have CV benefit for Type 1 Diabetes ?magdy elmasry
T1D Exchange , average A1C levels have not improved .How can adjunctive therapies ( added to insulin ) can help?
The Removal Trial.Three main clinical trials :
DEPICT with dapagliflozin ,
EASE with empagliflozin , and
inTANDEM with sotagliflozin.
Seminario 6 Empagliflozin, cardiovascular outcomes, and mortality in type 2 d...Mijail JN
This document summarizes a clinical trial that studied the effects of empagliflozin, an inhibitor of sodium-glucose cotransporter-2, on cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular events. A total of 7020 patients were randomly assigned to receive either 10 mg or 25 mg of empagliflozin or a placebo once daily for a median of 3.1 years. The trial found that empagliflozin reduced the primary composite outcome of cardiovascular death, non-fatal heart attack or non-fatal stroke compared to placebo, as well as reducing rates of death from any cause, death from cardiovascular causes, and hospitalization for heart failure. Genital infections were more common
This document discusses diabetic neuropathy. It begins with some global statistics on the prevalence and costs of diabetic neuropathy. It then discusses the pathology, risk factors, presentations, diagnosis and treatments of various types of diabetic neuropathy, including diffuse symmetrical sensorimotor polyneuropathy, autonomic neuropathy, and diffuse small fibre neuropathy. Tight glycemic control is emphasized as an important part of prevention and treatment.
This document discusses dysglycemia and chronic kidney disease (CKD). It begins with an agenda that covers background, pathophysiology, glycemic control, and insulin therapy and conclusions. It then discusses how diabetes is the most common cause of end-stage renal disease. It explains how dysglycemia includes sustained hyperglycemia and acute glucose fluctuations. The kidney plays an important role in glucose homeostasis by filtering, reabsorbing, and producing glucose. Both hyperglycemia and glucose variability can drive diabetic kidney disease through various pathways like protein kinase C activation and oxidative stress. Maintaining good glycemic control through lowering HbA1c can significantly reduce microvascular and cardiovascular complications in patients with CKD.
The document discusses cardiovascular risk and management in patients with diabetes, including treating cardiovascular risk factors as aggressively in diabetic patients as in non-diabetic patients with prior heart attacks, aiming for tighter glycemic control to reduce cardiovascular events and mortality, and considering individual patient factors and comorbidities when setting glycemic targets and selecting antihyperglycemic therapies, particularly in acute care settings where basal insulin regimens are preferred over sliding scales.
Dyslipidemia-latest guidlines-Review of Guidlines by Dr.Jayasoorya p gjpgkmr
Dyslipidemia newer guidelines
2019 ESC/EAS GUIDLINES FOR MANAGEMENT OF DYSLIPIDEMIA
2019 JUNE UPDATED AMERICAN COLLEGE OF CARDIOLOGY GUIDLINES FOR MANAGEMENT OF DYSLIPIDEMIA
This document provides information on antihypertensive drugs. It begins by listing the specific learning objectives, which include defining hypertension, discussing types and drugs for treatment, mechanisms of action, adverse effects, and considerations for use in various conditions. It then covers primary and secondary hypertension, urgency vs emergency, and mnemonics for drug classes. Individual drug classes are discussed in detail, including diuretics, ACE inhibitors, ARBs, calcium channel blockers, arteriolar vasodilators, and beta blockers. Mechanisms, advantages, disadvantages, and special considerations are provided for each class.
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
This document discusses different types of iatrogenic (medically induced) diabetes, including:
1) Pancreatogenic diabetes caused by pancreatic diseases or procedures that damage the pancreas.
2) Drug-induced diabetes caused by medications like corticosteroids, antipsychotics, immunosuppressants, protease inhibitors, and chemotherapy drugs.
3) Post-transplant diabetes that develops in some organ transplant recipients due to immunosuppressant drugs and other risk factors.
The document provides details on the mechanisms and risk factors for each type of iatrogenic diabetes.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
DKD is a leading cause of ESRD in the US, affecting 30-40% of those with diabetes. Poor glycemic control and hypertension are major risk factors for developing and progressing DKD. Clinical trials have shown that intensive control of blood glucose and blood pressure can delay and prevent kidney disease. New drugs targeting the kidney are showing promise in reducing albuminuria and slowing kidney function decline in DKD patients.
This document summarizes diabetic kidney disease (DKD), the leading cause of end-stage renal disease in the United States. DKD risk factors include age, sex, race, family history, hypertension, and poor glycemic control. Intensive glucose and blood pressure control can delay DKD progression. While current therapies can slow DKD, innovation is still needed to improve outcomes given residual risks. Novel drug classes targeting DKD mechanisms may provide future treatment options.
Diabetic nephropathy is a clinical syndrome characterized by the following :
Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least 2 occasions 3-6 months apart.
Progressive decline in the glomerular filtration rate (GFR).
Elevated arterial blood pressure.
Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy:
First, mesangial expansion is directly induced by hyperglycemia, perhaps via increased matrix production or glycation of matrix proteins.
Second, thickening of the glomerular basement membrane (GBM) occurs.
Third, glomerular sclerosis caused by intraglomerular hypertension (induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli).
These different histologic patterns appear to have similar prognostic significance.
Several issues are key in the medical care of patients with diabetic nephropathy.
These include glycemic control, management of hypertension, and reducing dietary salt intake and phosphorus and potassium restriction in advanced cases.
A meta-analysis from the Cochrane Database shows a large fall in blood pressure with salt restriction, similar to that of single-drug therapy
Chronic kidney disease (CKD) is defined as gradual loss of kidney function over months to years. Key risk factors include diabetes, hypertension, family history, and smoking. CKD is usually asymptomatic in early stages. Treatment focuses on controlling blood pressure and blood glucose, limiting proteinuria, treating anemia and bone disease, and slowing progression. The goals are to delay complications by optimizing blood pressure control with ACE inhibitors, ARBs, and other agents and managing associated conditions like anemia, dyslipidemia, mineral bone disorders.
Diabetic nephropathy is the leading cause of end-stage renal disease in the US. It is a microvascular complication of diabetes characterized by albuminuria and declining renal function. Risk factors include hypertension, hyperglycemia, family history, smoking, and certain ethnicities. Treatment focuses on tight glycemic and blood pressure control using ACE inhibitors or angiotensin receptor blockers to reduce proteinuria and slow renal decline. Early screening and aggressive management can help prevent or delay end-stage renal disease from diabetic nephropathy.
- The prevalence of diabetes and prediabetes in India is estimated to be 9.3% and 24.5% respectively by 2022, with nearly half of those with diabetes unaware of their condition.
- Lifestyle interventions like achieving 7% weight loss through diet and exercise can reduce the risk of developing type 2 diabetes by 58%. Metformin and other drugs may also help prevent diabetes.
- Glycemic control is important and should be assessed regularly through A1C or other tests. An A1C under 7% is a reasonable goal for many adults to reduce health risks.
- Other comorbidities like hypertension, obesity, and kidney disease also need to be managed through lifestyle changes,
- The CANVAS Program studied the effects of canagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes. It found that patients treated with canagliflozin had a lower risk of cardiovascular events, hospitalization for heart failure, and progression of kidney disease compared to placebo. However, canagliflozin was also associated with a higher risk of leg and foot amputations. The study provides support for the cardiovascular and renal protective effects of SGLT2 inhibitors like canagliflozin.
1) Diabetic nephropathy is characterized by persistent albuminuria, declining GFR, and presence of retinopathy. It involves thickening of basement membranes and expansion of the mesangial matrix.
2) It progresses through five stages from hyperfiltration to end-stage renal disease. Glycemic control, blood pressure management, and ACE inhibitors or ARBs can slow its progression.
3) Treatment involves tight glycemic and blood pressure control, lipid lowering, dietary protein restriction, anemia management, and renal replacement therapy through hemodialysis, peritoneal dialysis, or transplantation if end-stage is reached.
1) Diabetic nephropathy is characterized by persistent albuminuria, declining GFR, and presence of retinopathy. It involves thickening of basement membranes and expansion of the mesangial matrix.
2) It progresses through five stages from hyperfiltration to end-stage renal disease. Glycemic control, blood pressure management, and ACE inhibitors or ARBs can slow progression.
3) For patients reaching end-stage renal disease, treatment options include hemodialysis, peritoneal dialysis, and kidney transplantation. Kidney transplantation has the best outcomes, but survival is still worse for diabetics than non-diabetics.
1. The diabtologist wished for an oral hypoglycemic agent that controls blood glucose without hypoglycemia.
2. He wished for it to be used as a first line drug or added to other commonly used drugs like metformin or insulin.
3. He wished for it to have significant cardiovascular benefits and minimal side effects.
4. The genie granted these wishes by presenting dapagliflozin, an SGLT2 inhibitor that meets all the criteria wished for.
The document discusses new trends in the management of diabetes in cardiac patients. It provides guidelines on glycemic targets and pharmacological therapy for type 2 diabetes. The recommended first-line treatment is metformin. Glycated hemoglobin (A1C) of less than 7% is a reasonable goal for many adults with diabetes, though some may require less or more stringent targets depending on individual factors. Combination therapy with oral medications and insulin is often needed to control blood sugar levels in type 2 diabetes.
The EMPA-REG Outcome trial studied the effects of empagliflozin, a SGLT2 inhibitor, on cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular events. Over 7000 patients were randomly assigned to receive 10 mg or 25 mg of empagliflozin or placebo. The primary outcome was a composite of death from cardiovascular causes, nonfatal heart attack or nonfatal stroke. The study found that patients receiving empagliflozin had a lower rate of the primary composite cardiovascular outcome and of death from any cause compared to placebo when added to standard care. Empagliflozin was also associated with weight loss, reduced blood pressure and lower rates of kidney disease progression without increasing risks
Empagliflozin, cardiovascular outcomes, and mortality in type 2 DMAnirudhya J
The EMPA-REG Outcome trial studied the effects of empagliflozin, a SGLT2 inhibitor, on cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular events. Over 7000 patients were randomly assigned to receive empagliflozin 10mg, empagliflozin 25mg or placebo. The primary outcome was a composite of death from cardiovascular causes, nonfatal heart attack or nonfatal stroke. The study found that patients receiving empagliflozin had a lower rate of the primary composite cardiovascular outcome and lower all-cause mortality compared to placebo when added to standard care. Empagliflozin was also associated with weight loss and reduced blood pressure without increased heart rate but risks
A 35-year-old man presents with vomiting bright red blood and is diagnosed with variceal bleeding from liver cirrhosis. Management includes airway protection, IV fluids, antibiotics, terlipressin, urgent endoscopy for banding or sclerotherapy. A 73-year-old woman reports increased thirst and weight loss and is found to have diabetes. Testing shows HbA1c of 6.5% confirming type 2 diabetes. Treatment begins with lifestyle changes and metformin. An 18-year-old presents confused with abdominal pain and ketoacidosis is diagnosed. Treatment involves IV fluids, insulin drip, and monitoring glucose and ketones until acidosis resolves.
The document discusses the "glucose triad" which refers to the relationship between HbA1c, fasting plasma glucose, and postprandial plasma glucose in glycemic control. It notes that while HbA1c has traditionally been the target, more recent studies show intensive control to reach very low HbA1c levels may be detrimental. The document explores how the relationship between the components of the glucose triad changes over time as diabetes progresses, with postprandial glucose being more influential at lower HbA1c levels and fasting glucose becoming more important at higher levels. Treatment should target both fasting and postprandial hyperglycemia simultaneously for optimal control.
This study evaluated the safety and efficacy of adding the SGLT2 inhibitor dapagliflozin to furosemide for treating decompensated heart failure in patients with type 2 diabetes and reduced ejection fraction. 100 patients were randomized to receive either dapagliflozin plus furosemide or placebo plus furosemide. The addition of dapagliflozin improved diuresis parameters, reduced body weight and dyspnea scores to a greater extent than furosemide alone, with minimal effects on renal function or electrolyte levels. The results indicate that dapagliflozin enhances the diuretic effect of furosemide and may improve outcomes for patients with heart failure
This document discusses the challenges of treating diabetes in patients with chronic kidney disease (CKD). It notes that diabetes is a leading cause of CKD and end-stage renal disease. While good glycemic control can prevent CKD progression, it is difficult to achieve in CKD patients due to changes in insulin metabolism and increased risk of hypoglycemia. The document reviews various classes of anti-diabetic medications and their safety in different stages of CKD. It concludes that treatment options are limited for patients with more advanced CKD and emphasizes individualizing therapy based on renal function.
Management of pulmonary artery hypertensionAdityaNag11
This document discusses the management of pulmonary artery hypertension. The goals of therapy are to prevent disease progression in stable patients through lifestyle changes and education, and to stabilize right-sided heart function, provide symptomatic relief, and improve hemodynamics in unstable patients. Treatment includes pharmacological therapies like prostanoids, endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate cyclase stimulators. Non-pharmacological options include oxygen supplementation and surgical interventions like balloon atrial septostomy and lung transplantation. Combination therapy with multiple drug classes may provide added benefits over monotherapy.
This document provides information on chronic kidney disease (CKD), including its definition, causes, stages, clinical assessment, complications, treatment, and management of associated conditions like hypertension and dyslipidemia. CKD is defined as kidney damage or decreased kidney function lasting 3 months or more. The three most common causes are diabetes, hypertension, and glomerular disease. CKD progresses through five stages depending on kidney damage severity and function level. Treatment focuses on slowing disease progression, managing complications, and reducing cardiovascular risk through blood pressure control, cholesterol lowering, and other measures.
Similar to NephMadness 2017: Diabetic Nephropathy Region (20)
Sunitinib for the pancreatic neuroendocrine tumors, Moh'd sharshirMoh'd sharshir
1) Pancreatic neuroendocrine tumors are rare tumors that arise in the pancreas and often spread to the liver. Surgery is the primary treatment but many tumors are inoperable or metastasize.
2) The study examined using the drug sunitinib to treat advanced pancreatic neuroendocrine tumors, as these tumors rely on angiogenesis facilitated by growth factors like VEGF.
3) In a phase 3 clinical trial, 171 patients were randomized to receive either sunitinib or a placebo pill daily. Sunitinib was shown to significantly extend progression-free survival compared to the placebo. Overall survival and response rates were also improved with sunitinib treatment.
Management of oncology emergencies, Mohh'd sharshirMoh'd sharshir
This document summarizes the management of oncologic emergencies, focusing on tumor lysis syndrome (TLS). TLS is caused by massive lysis of tumor cells, releasing potassium, phosphate and uric acid. It is classified based on laboratory and clinical criteria. Risk is highest in Burkitt lymphoma, ALL and other high-grade lymphomas. Prevention focuses on IV hydration and hypouricemic agents like rasburicase or allopurinol. Electrolyte abnormalities are managed based on their severity. High-risk patients receive aggressive prevention while intermediate-risk patients generally receive allopurinol prevention.
Early goal-directed therapy in severe sepsis and septic shock: ProCESS, ARISE...Moh'd sharshir
1) This study compared early goal-directed therapy (EGDT) to usual care in patients with septic shock. EGDT aimed to optimize tissue oxygen delivery through monitoring of physiological targets like central venous pressure and central venous oxygen saturation.
2) The study found no significant difference in 90-day mortality between the EGDT and usual care groups. Patients in the EGDT group received more intravenous fluids and vasopressors but this did not impact mortality outcomes.
3) The study concludes that EGDT did not decrease mortality in patients presenting with septic shock compared to usual resuscitation practices. The value of incorporating EGDT into international guidelines is questionable.
Bathing of critically ill patients with chlorhexidine decreases hospital acqu...Moh'd sharshir
This meta-analysis examined the effect of daily bathing with chlorhexidine on hospital-acquired bloodstream infections in critically ill patients. The analysis found that daily chlorhexidine bathing reduced the risk of hospital-acquired bloodstream infections by 18% and was most effective at reducing gram-positive infections and catheter-related bloodstream infections when used with intranasal mupirocin. However, chlorhexidine bathing did not significantly impact gram-negative bacteria or fungal infections. The analysis concluded that chlorhexidine bathing may be an effective strategy to reduce healthcare-associated infections when combined with other preventative measures.
Case presentation, meningitis and treatment, Moh'd SharshirMoh'd sharshir
Meningitis is an inflammation of the meninges, the membranes surrounding the brain and spinal cord. It is caused by bacterial, viral, or fungal infections. The classic symptoms are fever, headache, and neck stiffness. Diagnosis involves examination of cerebrospinal fluid which shows increased white blood cells and decreased glucose levels in bacterial meningitis. Treatment depends on the identified pathogen but generally involves antibiotics. Adjunctive steroids may reduce complications for some types of bacterial meningitis. Outcomes vary depending on the cause, but bacterial meningitis can have mortality rates around 20% even with treatment.
Aortic dissection, pathophysiology, risk, incidence, types and treatment, Moh...Moh'd sharshir
This document presents a case of a 55-year-old man with a history of diabetes, hypertension, and prior stroke who was transferred for endovascular aortic repair after a motor vehicle accident caused multiple injuries including head trauma, chest trauma, cardiac contusion, aortic injury, and bone fractures. On examination, he was intubated and sedated. Imaging showed aortic pseudoaneurysm, lung effusions, and subcutaneous emphysema. The document then reviews aortic dissection including types, risk factors, clinical manifestations, diagnosis, and involvement of the ascending versus descending aorta.
This document summarizes adjuvant chemotherapy for resectable non-small cell lung cancer (NSCLC). It discusses that patients with stage I-IIIA NSCLC have a risk of recurrence even after surgery. Large clinical trials have found that platinum-based adjuvant chemotherapy can improve outcomes for completely resected NSCLC. Specifically, the IALT trial found that cisplatin-based chemotherapy improved 5-year survival from 40.4% to 44.5% compared to observation alone. The JBR.10 trial found that vinorelbine and cisplatin improved 5-year survival from 54% to 69% compared to observation. The CALGB 9633 trial initially found paclitaxel/carboplatin improved outcomes but
A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD, ...Moh'd sharshir
Vitamin D deficiency is common in CKD patients and linked to increased cardiovascular disease risk. This study found that cholecalciferol supplementation in nondiabetic CKD patients with vitamin D deficiency significantly improved brachial artery flow-mediated dilation and pulse wave velocity, markers of endothelial function and arterial stiffness respectively, over 16 weeks. Biomarkers of endothelial function, inflammation, and vascular calcification also improved. These results provide evidence that correcting vitamin D deficiency reduces cardiovascular risk in CKD patients.
kidney disease in HIV-positive patients, Moh'd sharshirMoh'd sharshir
Patients with HIV are at risk for both acute kidney injury and chronic kidney disease due to various factors like medication toxicity, HIV-associated nephropathy, and immune complex kidney diseases. The risk factors for acute kidney injury in HIV patients are similar to the general population but also include factors specific to HIV like low CD4 count and co-infection with hepatitis C virus. Timely screening for chronic kidney disease is important in HIV patients to monitor for decline in kidney function and proteinuria, in order to guide management and reduce risk of end-stage renal disease.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes, Moh'd sharshirMoh'd sharshir
This document summarizes the LEADER clinical trial which assessed the long-term cardiovascular safety of the diabetes drug liraglutide. The trial involved over 9,000 patients with type 2 diabetes at high risk of cardiovascular disease who were randomly assigned to receive either liraglutide or a placebo over a follow-up period of 3-5 years. The primary outcome was a composite of death from cardiovascular causes, non-fatal heart attack or non-fatal stroke. The results showed that liraglutide was associated with a lower rate of the primary composite outcome compared to placebo.
Therapy of focal or diffuse proliferative lupus nephritis, Moh'd sharshirMoh'd sharshir
Immunosuppressive therapy is recommended for patients with diffuse or focal proliferative lupus nephritis (LN). The standard induction therapies are cyclophosphamide or mycophenolate mofetil combined with glucocorticoids. Mycophenolate mofetil may be preferred in certain groups due to its comparable efficacy and better safety profile. Rituximab combined with mycophenolate mofetil and glucocorticoids has also shown efficacy in treating proliferative LN. Calcineurin inhibitors and other novel agents are being studied but cyclophosphamide and mycophenolate mofetil remain the standard of care.
Multitarget Therapy for InductionTreatment of Lupus Nephritis, Moh'd sharshirMoh'd sharshir
This study compared the efficacy and safety of a multitarget regimen consisting of tacrolimus, mycophenolate mofetil (MMF), and steroids to intravenous cyclophosphamide (IVCY) and steroids as induction therapy for lupus nephritis (LN). 368 patients with LN were randomly assigned to receive either the multitarget regimen or IVCY. The multitarget regimen resulted in significantly higher rates of complete remission and overall response. Adverse events were similar between groups. The multitarget regimen was found to be superior to IVCY as induction therapy for LN.
Novel oral anticoagulants in CKD review, Moh'd sharshirMoh'd sharshir
This document discusses the use of novel oral anticoagulants (NOACs) for stroke prevention and venous thromboembolism in patients with chronic kidney disease (CKD). It reviews recent trials that have re-analyzed data focusing on patients with reduced kidney function. Network meta-analyses found that NOACs were associated with lower risks of stroke, systemic embolism, and major bleeding compared to warfarin in CKD patients. Observational studies also suggest NOACs like apixaban, rivaroxaban, and dabigatran are similar or superior alternatives to warfarin for safety and efficacy in real-world CKD populations. However, more research is still needed, as
Delayed Graft Function post kidney transplant, Moh'd sharshirMoh'd sharshir
Induction therapy with anti-thymocyte globulin (ATG) may decrease the risk of delayed graft function (DGF) in deceased donor kidney transplant recipients by ameliorating ischemia reperfusion injury. A retrospective study of 76 mated kidney transplants found a non-significant 35% decrease in the odds of DGF when ATG was used compared to basiliximab. Larger prospective studies are still needed to confirm ATG's potential protective effect against DGF.
1) This study conducted a systematic review and meta-analysis of 23 studies to examine the effects of chronic kidney disease (CKD) on pregnancy outcomes and the effects of pregnancy on renal outcomes in women with CKD.
2) The results showed that women with CKD faced significantly higher risks of adverse pregnancy outcomes like preeclampsia, premature birth, and small-for-gestational-age babies compared to women without CKD.
3) However, the study found no evidence that pregnancy led to worsening of renal outcomes in women with CKD compared to non-pregnant women with CKD. Pregnancy did not appear to negatively impact kidney function or progression to kidney failure.
Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive biomarker for detecting kidney transplant rejection. This study evaluated dd-cfDNA levels in 384 kidney transplant patients. Dd-cfDNA levels were significantly higher in patients with active rejection compared to those without rejection. Dd-cfDNA discriminated active rejection with 85% specificity and 59% sensitivity. Dd-cfDNA also strongly discriminated antibody-mediated rejection from no rejection, with 83% specificity and 81% sensitivity. In contrast, serum creatinine did not provide any discrimination of rejection status. This study suggests dd-cfDNA may enable noninvasive detection and monitoring of kidney transplant rejection.
Nephrogenic systemic fibrosis (NSF) is a severe skin condition seen in patients with kidney failure exposed to gadolinium-based contrast agents. The document discusses the clinical features and pathogenesis of NSF and provides recommendations to minimize the risk of NSF in patients with kidney disease requiring gadolinium imaging. It is recommended that gadolinium be avoided in patients with eGFR <30 mL/min or on dialysis unless absolutely necessary. For patients who must receive gadolinium, a macrocyclic agent at the lowest possible dose is preferred, and hemodialysis should be performed within hours after administration.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
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3. ACEi and ARB for Nephroprotection
• ACE inhibitors and angiotensin receptor blockers have
been the reigning champs in diabetic nephropathy for
over 2 decades.
• The critical role of the renin angiotensin system (RAS) in
diabetic nephropathy has been extensively studied and
well-summarized in many reviews.
4. ACEi and ARB for Nephroprotection
• Overall, since the importance of RAS inhibition in
diabetic nephropathy was discovered there appears to
be a slowing of the incidence of ESRD from diabetic
nephropathy.
6. ACEi and ARB for Nephroprotection
• In type 1 DM: angiotensin-converting enzyme (ACE)
inhibitors have been studied in both early and late in the
course of diabetic nephropathy.
• Early in the course of diabetic kidney disease, when
moderately increased albuminuria is the only clinical sign
of a problem, captopril decreased the rate of albuminuria
excretion as well as the risk of progression to overt
diabetic nephropathy when compared to placebo.
Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group.Diabetologia. 1996 May;39(5):587-93
7. ACEi and ARB for Nephroprotection
• The Collaborative Study Group found that in subjects
who already had overt diabetic nephropathy, treatment
with captopril:
Slowed the rate of GFR decline.
Decreased the risk of ESRD.
and in some cases led to long term remission of
nephrotic syndrome and preservation of kidney function.
9. ACEi and ARB for Nephroprotection
• In type 2 DM: angiotensin receptor blockers (ARBs) have
been shown to have clear renoprotective effects in overt
diabetic nephropathy.
10. ACEi and ARB for Nephroprotection
• IDNT randomized 1715 subjects with hypertension and
overt nephropathy to irbesartan 300 mg/day, amlodipine
10 mg/day, and placebo.
• At a mean follow up of 2.6 years.
• The group treated with irbesartan had a significantly
lower risk of doubling serum creatinine or progression to
ESRD than the other groups.
11. ACEi and ARB for Nephroprotection
• The RENAAL trial compared losartan to placebo in 1513
subjects with overt diabetic nephropathy.
• Treatment with losartan reduced the risk of doubling of
serum creatinine and progression to ESRD at a mean
follow up of 3.4 years.
13. ACEi and ARB for Nephroprotection
• ACE inhibitors have also shown benefits in type 2 DM.
• The ADVANCE trial ( Action in Diabetes and Vascular disease:
preterAx and diamicroN-MR Controlled Evaluation study).
• Compared the combination of perindopril-indapamide to
placebo in over 11,000 subjects with type 2 DM.
15. ACEi and ARB for Nephroprotection
• The DETAIL trial compared the ACE inhibitor Enalapril to
the ARB Telmisartan in subjects with early diabetic
nephropathy.
• Found that Telmisartan was not inferior to Enalapril in
providing renoprotection.
16. Conclusions: Telmisartan is not inferior to enalapril in
providing long-term renoprotection in persons with type
2 diabetes.
17. ACEi and ARB for Nephroprotection
• VA Nephron-D: Trial where the combination of treatment
with losartan and lisinopril led to a significant increase in
adverse events and no improvement in mortality or
slowing of CKD progression when compared to
treatment with losartan alone.
18.
19. ACEi and ARB for Nephroprotection
• ACEi or ARB are clearly indicated in the treatment of
diabetic nephropathy, but are not always tolerated due to
side effects of hyperkalemia or hypotension.
21. Glycemic Control
• In diabetes there is nothing as fundamental than
hyperglycemia.
• If one does not have DM, one cannot develop diabetic
nephropathy (even though nodular glomerulosclerosis
that looks like diabetic nephropathy that has been found
in metabolic syndrome without overt diabetes).
• While type 1 DM and type 2 DM have different
pathogenesis, the end result of both is hyperglycemia.
22. Glycemic Control
• Hyperglycemia has been shown to activate the intrarenal
RAS system which plays an important role in the
development of diabetic nephropathy.
• Logically, it should follow that good glycemic control is a
critical part of the treatment of diabetic nephropathy.
23. Glycemic Control
• The landmark DCCT definitively showed the importance
of early glycemic control in subjects with type 1 DM.
• DCCT randomized subjects to a target A1C of 7% vs 9%
and included 1,365 subjects with normal albumin
excretion at baseline.
• The tight glycemic control group had a significant
reduction in the onset of albuminuria.
24.
25. Glycemic Control
• The long term follow up of DCCT, the EDIC study, found
that the renoprotective effects of a lower glycemic target
were sustained long term.
• Eight years after DCCT was completed, subjects initially
assigned to the intensive glycemic control group
continued to have a lower risk of development of
albuminuria.
26.
27. Glycemic Control
• 16 years after DCCT was completed they were less
likely to have developed impaired renal function.
• After the completion of the study all patients had the
same therapy and the hemoglobin A1c of the two groups
were indistinguishable (7.9 ±1.1 for the intensive therapy
group and 8.0 ±1.0 in the conventional therapy group).
29. Glycemic Control
• Patients with type 1 DM who already have moderately
increased albuminuria also appear to benefit from
intensive glycemic control, although the data is less
definitive given its small size.
• The 73 subjects with moderately increased
albuminuria at baseline in the DCCT had similar benefits
to those without albuminuria at baseline.
30. Glycemic Control
• A meta-analysis of smaller, earlier trials also suggests
benefits to intensive glycemic control in the setting of
already established, moderately increased albuminuria.
Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes, Lancet. 1993 May 22;341(8856):1306-9
31. Glycemic Control
• Once severely increased albuminuria has developed in
type 1 DM, most of the data comes in the setting of
multiple small studies of subjects who have become
normoglycemic after receiving pancreas transplants.
• Pancreas transplant led to a reduction in albuminuria in
one study at a year post transplant, and in another study
led to improvement of biopsy findings in diabetic
nephropathy at 10 years, but not at 5 years post-
pancreas-transplant.
32.
33. Glycemic Control
• In type 2 DM the data is less concrete.
• The UKPDS trial found that subjects with newly
diagnosed type 2 DM who were treated with intensive
glucose control did not have improved renal outcomes.
------> Intensive blood-glucose control by either
sulphonylureas or insulin substantially decreases the risk
of microvascular complications, but not macrovascular
disease, in patients with type 2 diabetes.
34. Glycemic Control
• The ADVANCE trial found a reduced risk of albuminuria,
but no reduction of the risk of doubling of serum
creatinine in subjects who had type 2 DM for an average
of 8 years.
35. Glycemic Control
• VADT: on the other hand, found a benefit only in tight
glycemic control for the risk of progression of
albuminuria from moderately increased to severely
increased.
36. Glycemic Control
• Then there is the ACCORD trial, which was stopped
early due to increased deaths (including increased
cardiovascular deaths) in the intensive treatment arm.
38. Sodium Glucose Lumen Transporter 2 (SGLT2)
inhibitors
• 2013 was also the year canagliflozin (Invokana) was
approved for sale in the United States, becoming the first
of a new wave of SGLT2 inhibitors for the treatment of
type 2 diabetes mellitus (DM).
• SGLT2 inhibitors have the beneficial effects of promoting
weight loss and avoiding hypoglycemia and
hyperinsulinemia. The currently available SGLT 2
inhibitors in the U.S. are:
39. Sodium Glucose Lumen Transporter 2 (SGLT2)
inhibitors
• SGLT2 reabsorbs Na+ and glucose in the proximal
convoluted tubule.
• SGLT2 inhibitors inhibit this transporter resulting in
glycosuria, decreased serum glucose, and increased
sodium delivery to the macula densa.
40. Sodium Glucose Lumen Transporter 2 (SGLT2)
inhibitors
• SGLT2 inhibitors may slow the progression of diabetic
nephropathy by decreasing hyperfiltration and by decreasing the
inflammatory and fibrotic response to hyperglycemia. This is
supported by data from animal and in vivo models.
• In vitro studies show that empagliflozin attenuates the inflammatory
and fibrotic effects of high glucose including expression of toll-like
receptor-4, nuclear deoxyribonucleic acid binding to NF-κB and
activator protein 1, collagen IV expression, and interleukin-6
secretion in human proximal tubule cells.
41. Sodium Glucose Lumen Transporter 2 (SGLT2)
inhibitors
• The recently completed EMPA-REG OUTCOME
trial compared empagliflozin to placebo in subjects with
type 2 DM with a history of CVD and a eGFR≥30
ml/min/1.73 m2.
43. Glucagon-like Peptide 1 (GLP-1) Receptor
Agonists
• GLP-1 is an incretin produced in the L-cells of the small
intestine in response to ingestion of food.
• GLP-1 lowers glucose through its actions on the GLP-1
receptor by stimulating pancreatic beta-cells to secrete
insulin, which in turn reduces plasma glucagon, slows
gastric emptying, and suppresses appetite.
44. Glucagon-like Peptide 1 (GLP-1) Receptor
Agonists
• The LEADER trial is a large, recently completed study
assessing cardiovascular outcomes in subjects with type
2 DM treated with liraglutide vs placebo.
• CONCLUSIONS:
-----> The rate of the first occurrence of death from
cardiovascular causes, nonfatal myocardial infarction, or
nonfatal stroke among patients with type 2 diabetes
mellitus was lower with liraglutide than with placebo.
-----> Subjects treated with liraglutide had a decreased risk
of new onset macroalbuminuria, although time to
persistent doubling of creatinine, ESRD, and death due
to renal disease were similar in both groups.
In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.
The active therapy group had lower risk of new onset of moderately increased albuminuria, less worsening of moderately increased albuminuria and less new onset or worsening of severely increased albuminuria.
Effect of Randomized Treatment on Renal Outcomes
A total of 1243 (22.3%) patients assigned active treatment and 1500 (26.9%) patients assigned placebo developed the composite renal outcome of new-onset microalbuminuria, new-onset nephropathy, doubling of serum creatinine above 200 μmol/L, or end-stage kidney disease (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.73 to 0.85; P < 0.0001; Table 4). On this basis, one such event would be prevented among every 20 (95% CI 15 to 30) patients assigned active treatment for a 5-yr period.
Active treatment also reduced the risk for progression of albuminuria among patients who had either normo- or microalbuminuria at baseline (HR 0.78; 95% CI 0.72 to 0.84; P < 0.0001) and the risk for new-onset microalbuminuria in patients with normoalbuminuria at baseline (HR 0.79; 95% CI 0.73 to 0.86; P < 0.0001; Table 4).
A total of 286 patients developed overt nephropathy, as defined by macroalbuminuria, during follow-up: 114 (2.1%) patients assigned active treatment and 163 (3.0%) patients assigned placebo (HR 0.69; 95% CI 0.54 to 0.88; P = 0.003). The relative risk reductions were of comparable magnitude in patients with normoalbuminuria or microalbuminuria at baseline (P = 0.3 for heterogeneity).
Regression of albuminuria was observed in more than half of all patients with micro- or macroalbuminuria at baseline, most of whom regressed to normoalbuminuria (Table 4). Proportionally more patients assigned active than assigned placebo treatment achieved restoration of normoalbuminuria (P = 0.006), with approximately similar absolute UACR declines according to treatment assignment (patients with microalbuminuria: from 55.0 to 10.6 μg/mg [active treatment] versus from 54.2 to 11.0 μg/mg [placebo]; patients with macroalbuminuria: from 490.6 to 9.0 μg/mg [active treatment] versus from 465.9 to 13.4 μg/mg [placebo]).
Active treatment reduced eGFR to a greater extent than placebo (P < 0.0001) in the first 4 mo (Figure 1), but annual declines in eGFR were similar in the active and placebo treatment groups thereafter (0.5 versus 0.6 ml/min per 1.73 m2). This was true for patients with normoalbuminuria (0.1 versus 0.0 ml/min per 1.73 m2; P = 0.69), patients with microalbuminuria (1.1 versus 1.4 ml/min per 1.73 m2; P = 0.45), and patients with macroalbuminuria (1.5 versus 2.7 ml/min per 1.73 m2; P = 0.34). Both end-stage kidney disease and doubling of serum creatinine to a level >200 μmol/L were infrequently observed in ADVANCE, and the occurrence of these two outcomes was not significantly different between randomly assigned groups (Table 4).
In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II–receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes.
Background Combination therapy with angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m2 of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥30 ml per minute per 1.73 m2 if the initial estimated GFR was ≥60 ml per minute per 1.73 m2 or a decline of ≥50% if the initial estimated GFR was
Will this be the year that the reigning champ in diabetic nephropathy cruises through the Filtered Four to sit at the top of the dance, or will the king be dethroned?
BACKGROUND
Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
Full Text of Background...
METHODS
A total of 1441 patients with IDDM -- 726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
Full Text of Methods...
RESULTS
In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of ≥ 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of ≥ 300 mg per 24 hours) by 54 percent (95 percent confidence interval, 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
Full Text of Results...
CONCLUSIONS
Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
BACKGROUND
Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
Full Text of Background...
METHODS
A total of 1441 patients with IDDM -- 726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
Full Text of Methods...
RESULTS
In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of ≥ 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of ≥ 300 mg per 24 hours) by 54 percent (95 percent confidence interval, 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
Full Text of Results...
CONCLUSIONS
Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
Patients with type 1 DM who already have moderately increased albuminuria also appear to benefit from intensive glycemic control, although the data is less definitive given its small size.
The 73 subjects with moderately increased albuminuria at baseline in the DCCT had similar benefits to those without albuminuria at baseline.
A meta-analysis of smaller, earlier trials also suggests benefits to intensive glycemic control in the setting of already established, moderately increased albuminuria.
Once severely increased albuminuria has developed in type 1 DM, most of the data comes in the setting of multiple small studies of subjects who have become normoglycemic after receiving pancreas transplants. Pancreas transplant led to a reduction in albuminuria in one study at a year post transplant, and in another study led to improvement of biopsy findings in diabetic nephropathy at 10 years, but not at 5 years post-pancreas-transplant.
Tight blood glucose control has been speculated to reduce late complications in insulin-dependent diabetics but results from individual studies have been inconsistent. We have done a meta-analysis of sixteen randomised trials of intensive therapy to estimate its impact on the progression of diabetic retinopathy and nephropathy and the risks of severe side-effects. In the intensive therapy group, the risk of retinopathy progression was insignificantly higher after 6-12 months of intensive control (odds ratio [OR] 2.11). After more than two years of intensive therapy the risk of retinopathy progression was lower (OR 0.49 [95% confidence interval 0.28-0.85], p = 0.011). The risk of nephropathy progression was also decreased significantly (OR 0.34 [0.20-0.58], p < 0.001). The incidence of severe hypoglycaemia increased by 9.1 episodes per 100 person-years (95% Cl -1.4 to +19.6) in the intensively treated patients. The incidence of diabetic ketoacidosis increased by 12.6 episodes per 100 person-years (95% Cl, 8.7-16.5) in the patients on continuous subcutaneous insulin infusion. Long-term intensive blood glucose control significantly reduces the risk of diabetic retinopathy and nephropathy progression but long-term continuous subcutaneous insulin infusion was associated with an increased incidence of diabetic ketoacidosis, and intensive therapy may cause more severe hypoglycaemic reactions.
Figure 2—Urinary protein excretion (A, C, E) and creatinine clearance (B, D, F) in pancreas transplant alone type 1 diabetic patients at baseline (pre-tx) and after 1 year (post-tx), subdivided in normoalbuminuric (A and B), microalbuminuric (C and D), and macroproteinuric (E and F) according to urinary protein at baseline. Full circles indicate albumin excretion rate before and after pancreas transplant alone in four microalbuminuric (C) and three macroalbuminuric (E) patients, and the respective creatinine clearance values (D and F).
Figure 1. Thickness of the Glomerular Basement Membrane, Thickness of the Tubular Basement Membrane, Mesangial Fractional Volume, and Mesangial-Matrix Fractional Volume at Base Line and 5 and 10 Years after Pancreas Transplantation. The mesangial fractional volume is the proportion of the glomerulus occupied by the mesangium; the mesangial-matrix fractional volume is the proportion of the glomerulus occupied by mesangial matrix. The shaded areas represent the normal ranges obtained in the 66 age- and sex-matched normal controls (means ±2 SD). Data for individual patients are connected by lines.
BACKGROUND:
Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.
METHODS:
3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.
FINDINGS:
Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).
INTERPRETATION:
Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)
Background In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. Methods We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. Results After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P
Background The effects of intensive glucose control on cardiovascular events in patients with longstanding type 2 diabetes mellitus remain uncertain. Methods We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene. Results The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group. Conclusions Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications, with the exception of progression of albuminuria (P=0.01).
Design—ACCORD is a parallel group, randomized trial designed to investigate whether intensive glycemic therapy with a target HbA1c of 291.7 micromol/L, or retinal photocoagulation or vitrectomy, and 2) these plus peripheral neuropathy. Thirteen prespecified secondary measures of kidney, eye, and peripheral nerve function were also evaluated. Randomization was performed at clinical sites using a central randomization routine available on the study website. Both investigators and participants were unmasked to treatment arm assignment. Results—A total of 10,251 participants were randomized (5,128 intensive and 5,123 standard) between January, 2001 and October, 2005. This analysis includes 10,234 patients (5,107 intensive and 5,108 standard). Intensive therapy was stopped before study end due to increased mortality, and patients were transitioned to standard therapy. Outcomes are reported at transition and at study end. At transition, the first composite outcome occurred in 443/5107 and 444/5108 participants in the intensive and standard arms, respectively (p= 0.99), and the second outcome in 1591/5107 and 1659/5108 participants in intensive and standard arms (p=0.20). Results were similar at study end. Secondary measures at study end favoring intensive therapy (p2.0 on the Michigan Neuropathy Screening Instrument, loss of ankle jerk and light touch. Conclusions—Intensive glycemic treatment did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of macroalbuminuria and some measures of eye complications and neuropathy. These benefits must be weighed against the increase in total and CVD-related mortality, increased weight gain, and higher risk for severe hypoglycemia.
This study found that treatment with empagliflozin reduced the risk of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarctions, and nonfatal strokes.
Analysis of prespecified secondary endpoints found that treatment with empagliflozin reduced the risk of progression to macroalbuminuria, risk of incident nephropathy, and doubling of serum creatinine.
he exact location of GLP-1 receptors in human kidneys is unclear. GLP-1 receptors have been found in rodent and porcine proximal tubular cells. In human kidneys they have only been found in hilar and intralobular arteries, but there is some methodological concern that currently available methods for detecting GLP-1 receptors are inaccurate. GLP-1 infused in obese men led to a significant increase in urinary sodium excretion, a decrease in proton excretion, and a decrease in the glomerular filtration rate suggesting an action at the level of the proximal tubule, perhaps at the level of the Na+/H+ exchanger. Rats with early type 1 diabetic nephropathy treated with the GLP-1 receptor exendin-4 had a decrease in albuminuria, glomerular hyperfiltration and a decrease in the release of pro-inflammatory cytokines. It is through these effects that GLP-1 agonists are hypothesized to have renoprotective effects in diabetic nephropathy.