My Nephrology Registrar Seminar Talk from September 2013
Topics Covered
Pathogenesis of Diabetic Nephropathy
Other Renal Disease in Diabetes
Treatment of Diabetic Kidney Disease + The Joint Renal Diabetic Clinic
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
My Nephrology Registrar Seminar Talk from September 2013
Topics Covered
Pathogenesis of Diabetic Nephropathy
Other Renal Disease in Diabetes
Treatment of Diabetic Kidney Disease + The Joint Renal Diabetic Clinic
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
- Visit our website for more lectures: www.NephroTube.com
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Effects of Sodium Glucose contransporter (SGLT2) inhibition on renal outcomes in patients with (diabetic) chronic kidney disease.
Presentation given during the East by Southwest, Annual Update in Nephrology, September 17th 2017, Santa Fe, NM
http://medicine.unm.edu/academic-divisions/nephrology/east-by-southwest.html
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
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
Effects of Sodium Glucose contransporter (SGLT2) inhibition on renal outcomes in patients with (diabetic) chronic kidney disease.
Presentation given during the East by Southwest, Annual Update in Nephrology, September 17th 2017, Santa Fe, NM
http://medicine.unm.edu/academic-divisions/nephrology/east-by-southwest.html
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
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Management of coronary disease in diabetes - Is it different?Dr Vivek Baliga
The management of diabetes and coronary artery disease go hand in hand. This presentation by Dr Vivek talks on whether it varies from usual management.
Mr. AH is a 70-year-old man who was diagnosed with T2DM 10 years ago. He was initially treated with lifestyle management and metformin.
3 years later, his doctors advised him to add long acting basal insulin analogue to metformin, reached to 40U/day .
Other current medical conditions include: hypertension, hypothyroidism, and mild osteoporosis without fracture history.
Current medications; Metformin 1000 mg bid, long acting basal insulin analogue 40U/day , Candesartan 16 mg qd, Alendronate 70 mg once weekly, Levothyroxine 100 mg qd.
Physical exam: BMI 26 kg/m2, BP 140/80 mmHg, otherwise unremarkable.
His current FPG 140 mg/dL and HbA1c 8.5%. Kidney and liver functions are normal.
Diabetes mellitus (DM) is a disease of inadequate control of blood levels of glucose. It has many subclassifications, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and steroid-induced diabetes. Type 1 and 2 DM are the main subtypes, each with different pathophysiology, presentation, and management, but both have a potential for hyperglycemia. This activity outlines the pathophysiology, evaluation, and management of DM and highlights the role of the interprofessional team in managing patients with this condition.
Objectives:
Describe the pathophysiology of diabetes mellitus.
Outline the epidemiology and risk factors of diabetes mellitus.
Review the treatment considerations and common complications of diabetes mellitus.
Identify the importance of improving collaboration and care coordination amongst the interprofessional team to enhance the delivery of care for patients affected by diabetes mellitus.
Access free multiple choice questions on this topic.
Go to:
Introduction
Diabetes mellitus is taken from the Greek word diabetes, meaning siphon - to pass through and the Latin word mellitus meaning sweet. A review of the history shows that the term "diabetes" was first used by Apollonius of Memphis around 250 to 300 BC. Ancient Greek, Indian, and Egyptian civilizations discovered the sweet nature of urine in this condition, and hence the propagation of the word Diabetes Mellitus came into being. Mering and Minkowski, in 1889, discovered the role of the pancreas in the pathogenesis of diabetes. In 1922 Banting, Best, and Collip purified the hormone insulin from the pancreas of cows at the University of Toronto, leading to the availability of an effective treatment for diabetes in 1922. Over the years, exceptional work has taken place, and multiple discoveries, as well as management strategies, have been created to tackle this growing problem. Unfortunately, even today, diabetes is one of the most common chronic diseases in the country and worldwide. In the US, it remains as the seventh leading cause of death.
Diabetes mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels. DM has several categories, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and secondary causes due to endocrinopathies, steroid use, etc. The main subtypes of DM are Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM), which classically result from defective insulin secretion (T1DM) and/or action (T2DM). T1DM presents in children or adolescents, while T2DM is thought to affect middle-aged and older adults who have prolonged hyperglycemia due to poor lifestyle and dietary choices. The pathogenesis for T1DM and T2DM is drastically different, and therefore each type has various etiologies, presentations, and treatments.
New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
Diabetes mellitus is a worldwide epidemic. Its prevalence is on a steep rise and is more pronounced in India making it the ‘diabetes capital of the world’. There is also a parallel increase in the prevalence of diabetic nephropathy and is now the single most common cause of end-stage kidney disease leading to significant morbidity and mortality as well as accounts for a tremendous burden on the health care costs. It is also shown that the presence of diabetes increases the risk and progression of non-diabetic kidney disease.
Euglycemic ketoacidosis: Missed complication of Diabetesiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Type 2 Diabetes Mellitus: The Concerned Complications and Target OrgansApollo Hospitals
Diabetes has been considered as the most dreaded non-communicable disease consuming the mankind rapidly. WHO has predicted the number of diabetics to be approximately 366 millions by 2030. The disease is characterized by hyperglycemia and the basic symptoms are polyphagia, polydipsia and polyuria. The autoimmune type 1 diabetes represent almost 1% of the total diabetic population, the rest being that of type 2 diabetes (T2D). Type 2 diabetes has been linked to a variety of factors such as heredity, environmental factors, unhealthy eating habits, sedentary lifestyle, stress etc. The uncontrolled hyperglycemia has profound deleterious effects on almost all the organs and results in various cardiovascular disorders, retinopathy, neuropathy, and nephropathy. Recent studies have revealed an array of pulmonary dysfunctions related with T2D ranging from respiratory defects to tuberculosis. Diabetes also predisposes the person to hepatic dysfunctions like NAFLD and HCC and a range of infections at various sites which are difficult to manage. Post-surgical infections are of special interest for subjects with uncontrolled hyperglycemia prior to surgery. Scientists all over the world are revealing different pathways and associated therapies for type 2 diabetes in order to control the pathological effects covering almost whole body physiology.
Fasting and Caloric Restriction Show Promise for Reducing Type 2 Diabetes Bio...Premier Publishers
The global epidemic of type 2 diabetes (T2D) and its co-morbidities threatens to overwhelm public health services and urgent patient intervention is necessary. A review of mainly randomised controlled trials investigating the reduction of biochemical T2D risk markers through fasting or caloric restriction (CR) found that in T2D or where baseline fasting glucose or HbA1c were elevated, there were significant improvements in fasting glucose and HbA1c, while fasting insulin and insulin resistance may show improvement regardless of condition or baseline levels. There may, however, be ethnic differences, with a clear positive correlation found only in Caucasians. Intermittent CR (i.e. non-continuous periods of fasting) is at least as effective as isocaloric continuous CR, while CR of 400-800 kcal/day is possibly more effective than higher levels for reducing fasting glucose and HbA1c. Time restricted feeding also shows promise but there are few human studies. The findings suggest that the optimum regimen to reduce biochemical risk markers for T2D is an intermittent fasting programme employing a very low-calorie diet with the longest possible number of consecutive days of fasting. The addition of liquid meal replacements, low carbohydrate CR and supplementation of vitamin D, ω-3 PUFAs and L-carnitine may also be of benefit.
Similar to Diabetes management in hemodialysis by prof alaa wafa (20)
Disturbances of piturtary adrenal gonadal axis in hemodialysis ptalaa wafa
The kidneys play an important role in hormonal management. Endocrine disorders are one of the most crucial elements of ‘uraemic syndrome’ which is underestimated and has not been fully examined.
In CRF, there are complex endocrinal disorders related to hypothalamus and pituitary functions, and their relations to adrenal and gonadal functions also as far as sex hormones and adipose tissue hormones .
There is a great need for more randomized clinical trials to evaluate new and old treatment approaches, with the goal of developing better evidence-based practice guidelines.
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
diabetes was associated with insulin resistant state which affects liver cells.Also fatty liver may be called NAFLA OR NASH may lead to liver cirrhosis and sometimes to hepatocelular carcinoma
Anti thyroid therapy like carbimazol,methimazol and propylethoiuracil may affect liver through affection of liver cell and can lead to cholestasis or liver cell failure
Fasting Ramadan carry many hazards to diabetic need to fast. Uncontrolled patients have a liability to some dangerous complications like DKA,HYPOGLYCEMIA,HHS AND thromboembolism
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Diabetes management in hemodialysis by prof alaa wafa
1. Diabetes Management in
Hemodialysis
BY
Alaa Wafa MD.
Associate Professor of internal medicine
Diabetes & Endocrine unit.
Mansoura university
8th international HD course
UNC 15/12/2015
2. AGENDA
2
Background of Dysglycemia and CKD
Pathophysiology of Dysglycemia and CKD
Glycemic control and CKD
Insulin therapy and CKD
Conclusions
3. TEAMWORK- the power of a
multidisciplinary approach
Patient and
family
Nephrologist
Nurse
Clinician
Diabetes
Educator
Pharmacist
Registered
Dietitian
Social
Work
5. Rate of kidney diseases in Egypt is 36.4* with about
5.19% deaths
*Per 100,000
http://www.worldlifeexpectancy.com/cause-of-death/kidney-
disease/by-country/ accessed 2012 Oct.
6. Dysglycemia
The Dysglycemia of diabetes includes two components:
• (1) sustained chronic hyperglycemia that exerts its effects
through both excessive protein glycation and activation of
oxidative stress
• (2) acute glucose fluctuations (glycemic variability).
Glycemic variability seems to have more deleterious effects than sustained
hyperglycemia in the development of diabetic complications as both upward
(postprandial glucose increments) and downward (interprandial glucose
decrements) changes activate the oxidative stress.
6
7. Glucose variability
Multiple fluctuations of glycemia in the same individual
within-day or day-to-day, or even over longer periods of
time; that is, week to-week or visit-to-visit.
The concept of glucose variability was first introduced in the
Diabetes Control and Complications Trial (DCCT), and
defined as the standard deviation (SD) of daily blood
glucose around the mean from each quarterly visit
8. Am J Kidney Dis 2002; 39:S1
What is CKD?
• Presence of markers of kidney damage for three
months, as defined by structural or functional
abnormalities of the kidney with or without decreased
GFR,
• Manifest by either pathological abnormalities or other
markers of kidney damage, including abnormalities in
the composition of blood or urine, or abnormalities in
imaging tests.
• The presence of GFR <60 mL/min/1.73 m2 for three
months, with or without other signs of kidney damage
as described above.
10. Uremia alters the entire metabolism including that
of carbohydrates, proteins and fats. It also causes
electrolyte disturbances and upsets mineral and
hormonal homeostasis. Directly or indirectly,
glucose metabolism is disturbed by all these
changes’.
Kumar, K.V. S. et al: Glycemic Control in Patients of Chronic Kidney Disease. www.ijddc.com/article.asp?issn=0973-
3939;year=2007; volume27; issue=4
International Journal of Diabetes in Developing Countries.
Diabetes and CKD
11. Chronic kidney disease (CKD) is associated with
insulin resistance and, in advanced CKD, decreased
insulin degradation.
The latter can lead to a marked decrease in insulin
requirement or even the cessation of insulin
therapy in patients with type 2 diabetes.
Both of these abnormalities are at least partially
reversed with the institution of dialysis
Kumar, K.V. S. et al: Glycemic Control in Patients of Chronic Kidney Disease. www.ijddc.com/article.asp?issn=0973-
3939;year=2007; volume27; issue=4
International Journal of Diabetes in Developing Countries.
Diabetes and CKD
12. Pathways within diabetes that lead to the development
of vascular disease
Glomerular endothelial dysfunction (in particular, damage to the
glycocalyx) is the likely step in initiating albuminuria1
This diagram shows the relationship between hyperglycaemia, insulin resistance, endothelial
dysfunction, macrovascular disease and albuminuria in diabetes.1,2
12
Notes on this diagram1:
Proposed major pathways are represented
by pink arrows.
Pathways of less certain significance are
represented by grey arrows.
In type 2 diabetes, other pathways not
directly involving endothelial dysfunction,
are likely in the pathogenesis of
macrovascular disease and may also
contribute to albuminuria (broken arrows).
Type 1 diabetes Type 2 diabetes
Cardiovascular
disease albuminuria
Insulin resistance
syndrome
Glucose
Effector pathways
Endothelial (including
glycocalyx) dysfunction
Reference:
1.Satchell SC and Tooke JE. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia. 2008;51:714-725. 2.Deckert T, et al.
Diabetologia. 1989;32(4):219-26.
13. Diabetic kidney disease implies widespread vascular
disease
• The epidemiology of albuminuria
(abnormal levels of albumin in the
urine) reveals a close association with
vascular disease1
• Meta-analyses in general population
and high risk cohorts demonstrated
that albuminuria is associated with
cardiovascular mortality
independently of traditional
cardiovascular risk factors2,3
• The presence of both generalised
vascular dysfunction and albuminuria
suggests a common cause of
proteinuria4
13
Reference:
1. Satchell SC and Tooke JE. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia. 2008;51:714-725. 2. Matsushita K,
van der Velde M, Astor BC, et al. Lancet 2010;375(9731):2073–2081 3. Gansevoort RT, Matsushita K, van der Velde M, et al. Kidney Int. 2011;80(1):93–104. 4. Deckert T, et
al. Diabetologia. 1989;32(4):219-26.
Hazard ratios (HR) and 95% confidence
intervals for cardiovascular mortality
according to ACR2
4
2
1
0.5
2.5 5 10 30 300 1000
HRforCVDmortality(ACRstudies)
ACR, mg/g
Adapted from Matsushita K, van der Velde M, Astor BC, et al. Lancet 2010;375:2073–2081.
14. These slides were sponsored by Janssen and developed in conjunction with the BRS CKD Strategy Group, following an advisory board that
was organised by Janssen. Bedrock Healthcare Communications provided editorial support to members of the advisory board in developing
the slides. Janssen reviewed the content for technical accuracy. The content is intended for a UK healthcare professional audience only.
JOB CODE PHGB/VOK/0914/0018b
Date of preparation: January 2015
Pathophysiology of
Dysglycemia & CKD
15. Functions of the kidney
15
Filtration and
reabsorption
Acid/base
balance
Electrolyte
Balance
Excretion of
toxic substances
Hormone production:
• Calcitrol (healthy bones)
• Renin (BP regulation)
• Erythropoieitin
(red blood cell production)
Glucose reabsorption
and gluconeogenesis
16. The kidneys’ contribution to glucose homeostasis
• Kidneys contribute to glucose homeostasis in many ways including:
producing, filtering, reabsorbing and excreting glucose
• The kidneys produce approximately 20-25%1,2 of the total endogenous
glucose production
• In a healthy individual* virtually all of the filtered glucose is actively
reabsorbed into the blood by the sodium glucose co-transporters 2 and
1 (SGLT2 and SGLT1); virtually none is excreted in the urine2,3
16
*Normal physiological blood glucose range <6.5mmol/L before meals and <7.8mmol/L after meals
References:
1. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab. 2000;2:345-50.
2. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010 Feb;27(2):136-42.
3. Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation. Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S66-72
17. The role of the kidney in glucose reabsorption
• There are two main sodium-glucose
cotransporters: SGLT2 and SGLT11
• SGLT2 is mainly found in the
proximal tubules of the kidneys1
• SGLT2 is responsible for
reabsorbing approximately 90%
of the glucose reabsorbed by
the kidney2
• The remaining glucose is
reabsorbed by SGLT1 further
along the proximal tubule1
• The reabsorbed glucose is then
returned to the blood2
17
Adapted from Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42.
Reference:
1. Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42. 2. DeFronzo RA, et al. Diabetes Obes Metab. 2012;14:5-14.
18. The role of the kidney in glucose reabsorption
18
~180L filtered per day by the kidney1
References:
1. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012
Jan;14(1):5-14.
2. Clifford J. Bailey. Medscape Education Diabetes & Endocrinology. The Role of the Kidney in Glucose Control.. CME Released: 02/26/2013 ; Valid for credit through
02/26/2014.
A normal kidney
A kidney in a patient
with type 2 diabetes
Average blood glucose of
~100mg/dL2
Average blood glucose of
~150mg/dL2
~180g of glucose filtered per
day2
No increase in SGLT2
cotransporters2
~250g of glucose filtered per
day2
glucose reabsorption and
elimination of glucose in the
urine2
Hyperglycaemia
Increase in SGLT2
cotransporters2
20. The role of the kidney in insulin elimination
• The kidney plays a central role in the metabolism of insulin1
• Increased insulin levels suppress gluconeogenesis in the
kidney and enhance glucose reuptake by the kidney2
• Six to eight units of insulin are degraded by a healthy
kidney each day1
– This is approximately 25% of the daily production of insulin by the
pancreas
20
References:
1. Palmer BF and Henrich WL Carbohydrate and insulin metabolism in chronic kidney disease.. Available at: http://www.uptodate.com/contents/carbohydrate-and-insulin-
metabolism-in-chronic-kidney-disease.
2. Andrianesis V and Doupis J. The Role of Kidney in Glucose Homeostasis - SGLT2 Inhibitors, a New Approach in Diabetes Treatment. Expert Rev Clin Pharmacol.
2013;6(5):519-539.
21. Renal Metabolism of Insulin
30–80% of systemic insulin is metabolized particularly in
the kidney .
The kidney is, therefore, the main organ responsible for
metabolizing exogenous insulin administered to diabetic
patients .
About 65% of insulin that reaches the kidney is filtered in
the glomerulus and is, subsequently, metabolized in the
proximal tubular cells.
About 35% of insulin diffuses from postglomerular
peritubular vessels to the contraluminal cell membrane of
the proximal tubular cell, where it is also degraded.
Less than 1% of filtered insulin appears in the urine
21
22. Renal Metabolism of Insulin
Unlike insulin, C-peptide is not metabolized
during its first pass through the liver and,
approximately 70%of its plasma clearance is
performed in the kidney For that reason,
serum concentration of C-peptide reflects
pancreatic liberation of endogenous insulin
in subjects with normal renal function
22
24. Hyperglycaemia drives diabetic kidney disease
1. Activation of protein kinase C1
2. Acceleration of the renin-
angiotensin-aldosterone
system (RAAS)1
3. Non-enzymatic glycation
that generates advanced
glycation end products1
– Circulating levels are
raised in people with
diabetes, particularly those
with renal insufficiency, since
they are normally excreted in
the urine1
• Oxidative stress seems to be a
theme common to all three
pathways3
24
Hypertension
Overproduction of
mesangial cell matrix
Tubulointerstitial
injury
Acceleration
of RAAS
Advanced glycation
end products (AGEs)
Protein kinase C and
growth factors
Glomerular
damage
ProteinuriaNephron loss
Hyperglycaemi
a
Reference:
1.Cade WT. Diabetes-Related Microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322–1335. 2.Wolf G et al. (2005) From the
periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54: 1626-1634. 3.Dronavalli S, Duka I
and Bakris GL. Nat Clin Pract Endocrinol Metab. 2008;4(8):444-52.
Three mechanisms have been postulated that explain how hyperglycaemia
causes tissue damage in the kidney:1-3
26. Dysglycemia drives diabetic kidney disease
• For instance, the urinary excretion rate of 8-iso-PGF2α, a
reliable marker of oxidative stress, was found to be strongly,
positively correlated (r = 0.86, p < .001) with glycemic variability
assessed from the mean amplitude of glycemic excursions
(MAGE) as estimated by continuous glucose monitoring
systems (CGMS).
These observations therefore raise the question of whether we
have the appropriate tools for assessing glycemic variability in
clinical practice ??????
26
27. Conclusions
The short-term glucose variability expressed by 2hPG-
FPG is closely associated with decreased eGFR and an
increased risk of CKD in patients with poor glycemic
control (HbA1c≥7%).
28.
29. • Patients with more variable HbA1c face a higher risk of microvascular
complications, in terms of the frequency and amplitude of HbA1c
fluctuation.
• The deleterious effect of glucose variability on the kidneys attributed
to the metabolic memory induced by repeated exposure to glucose
fluctuation.
• The precise mechanism has not been well determined; however,
endothelial dysfunction and oxidative stress were found to be
worsened by glucose variability compared with stable hyperglycemia,
and could be reversed by Reduction of glucose fluctuations.
30. • Patients lagged in the ‘metabolic memory’ as
a result of frequent HbA1c fluctuation with a
large rang were much more prone to
developing severe nephropathy than those
with the same average HbA1c, but less
variable HbA1c.
31.
32. Conclusions.
Subjects with CKD and T2DM had poor glycemic control and
significantly higher glycemic variability comparative to those without
CKD, and especially to healthy volunteers. Assessment of glycemic
variability indices through CGM is more accurate than HbA1c for
the quantification of glycemic control in CKD diabetic patients
33. AGENDA
33
Background of Dysglycemia and CKD
Pathophysiology of Dysglycemia and CKD
Glycemic control and CKD
Insulin therapy and CKD
Conclusions
34. Glycemic control and CKD
-50
-40
-30
-20
-10
0
Diabetes-
related death
Myocardial
infarction
Microvascular
complications
Peripheral
vascular
disease
Lowering HbA1c by 1% significantly reduces:
Reductioninincidencerisk
per1%reductioninHbA1c
–21%*
–14%*
–37%*
–43%*
*p < 0.0001
Stratton IM et al. BMJ 2000;321:405–12
35. Value of Glycaemic Control in Diabetics with CKD
Preserving renal function,
Avoiding the progression of CKD
Reducing cardiovascular complications and
those secondary to diabetes
Decreasing the mortality rate in CKD
patients, both in predialysis and dialysis
35
36. Glycaemic Control in Diabetics with CKD
Diabetic Nephropathy
36
Diabetes, Obesity and Metabolism, 10,2008 , 811–823
37. Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update toa Position Statement of theAmericanDiabetesAssociation(ADA) and the
EuropeanAssociationfor the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
38. Healthy eating, weight control, increased physical activity & diabetes education
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
high
low risk
gain
edema, HF, fxs
low
Thiazolidine-
dione
intermediate
low risk
neutral
rare
high
DPP-4
inhibitor
highest
high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-
dione
+
SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-ior
or
or GLP-1-RA
high
low risk
loss
GI
high
GLP-1 receptor
agonist
Sulfonylurea
high
moderate risk
gain
hypoglycemia
low
SGLT2
inhibitor
intermediate
low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor
agonist
+
SGLT-2
Inhibitor
+
SU
TZD
Insulin§
Metformin
+
Metformin
+
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono-
therapy
Efficacy*
Hypo risk
Weight
Side effects
Costs
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
Triple
therapy
or
or
DPP-4
Inhibitor
+
SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable
therapy‡
GLP-1-RAMealtime Insulin
Insulin (basal)
+
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
HbA1c
≥9%
Metformin
intolerance or
contraindication
Uncontrolled
hyperglycemia
(catabolic features,
BG ≥300-350 mg/dl,
HbA1c ≥10-12%)
43. Antihyperglycemic agents and CKD
Diabetes mellitus (DM) is the leading cause of chronic
renal failure (CRF) and dialysis therapy . Numerous
drugs with different mechanism of action may serve to
reduce both acute and chronic diabetic complications as
well as to improve the quality of life in diabetic patients
In patients with CKD, therapeutic
possibilities are limited because of reduction in glomerular
filtration rate (GFR) that is accompanied by accumulation
of some oral agents and/or their metabolites
43
46. AGENDA
46
Background of Dysglycemia and CKD
Pathophysiology of Dysglycemia and CKD
Glycemic control and CKD
Insulin therapy and CKD
Conclusions
47. Currently Available Insulin Products
Insulin* Onset Peak Effective
Duration
Rapid-Acting
Aspart, Glulisine, Lispro
5-15 minutes 30-90 minutes <5 hours
Short-Acting
Regular, U-500
30-60 minutes 2-3 hours 5-8 hours
Intermediate (basal)
NPH
2-4 hours 4-10 hours 10-16 hours
Long-Acting (basal)
Glargine, Detemir
2-4 hours** No peak 20-24 hours
Premixed
75% NPL/25% Lispro
50% NPL/50% Lispro
70% Aspart Protamine/30%
Aspart
70% NPH/30%
regular/NPH
5-15 minutes
5-15 minutes
5-15 minutes
30-60 minutes
Dual
Dual
Dual
Dual
10-16 hours
10-16 hours
10-16 hours
10-16 hours
*Assumes 0.1-0.2 units/kg/injection. Onset and duration may vary significantly by injection site.
** Time to steady state
DeWitt DE, et al. JAMA. 2003; Hirsch IB, et al. Clinical Diabetes. 2005.
48. • Start: 10U/day or 0.1-0.2 U/kg/day
• Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
• For hypo: Determine & address cause;
ê dose by 4 units or 10-20%.
Basal Insulin
(usually with metformin +/-
other non-insulin agent)
Figure 3.
Approach
to starting
& adjusting
insulin in
T2DM
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
49. Add ≥2 rapid insulin* injections
before meals ('basal-bolus’†
)
Change to
premixed insulin* twice daily
Add 1 rapid insulin* injections
before largest meal
• Start: Divide current basal dose into 2/3 AM,
1/3 PM or 1/2 AM, 1/2 PM.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 10U/day or 0.1-0.2 U/kg/day
• Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
• For hypo: Determine & address cause;
ê dose by 4 units or 10-20%.
Basal Insulin
(usually with metformin +/-
other non-insulin agent)
If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin.
(Consider initial
GLP-1-RA
trial.)
If not
controlled,
consider basal-
bolus.
If not
controlled,
consider basal-
bolus.
• Start: 4U, 0.1 U/kg, or 10% basal dose. If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 4U, 0.1 U/kg, or 10% basal dose/meal.‡
If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
Figure 3.
Approach
to starting
& adjusting
insulin in
T2DM
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
50. Add ≥2 rapid insulin* injections
before meals ('basal-bolus’†
)
Change to
premixed insulin* twice daily
Add 1 rapid insulin* injections
before largest meal
• Start: Divide current basal dose into 2/3 AM,
1/3 PM or 1/2 AM, 1/2 PM.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 10U/day or 0.1-0.2 U/kg/day
• Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
• For hypo: Determine & address cause;
ê dose by 4 units or 10-20%.
Basal Insulin
(usually with metformin +/-
other non-insulin agent)
If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin.
(Consider initial
GLP-1-RA
trial.)
low
mod.
high
more flexible less flexible
Complexity
#
Injections
Flexibility
1
2
3+
If not
controlled,
consider basal-
bolus.
If not
controlled,
consider basal-
bolus.
• Start: 4U, 0.1 U/kg, or 10% basal dose. If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 4U, 0.1 U/kg, or 10% basal dose/meal.‡
If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
Figure 3.
Approach
to starting
& adjusting
insulin in
T2DM
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
51. Lifestyle changes plus metformin (± other agents)
Basal
Add basal insulin
Basal Plus
Add prandial insulin at main meal
Basal Bolus
Add prandial insulin before each meal
Progressive deterioration of -cell function
Basal Plus: once-daily basal insulin
plus once-daily* rapid-acting insulin
Matching treatment to disease progression using a
stepwise approach
*As the disease progresses, a second daily injection of glulisine may be added
Adapted from Raccah D, et al. Diabetes Metab Res Rev 2007;23:257–64
Proper Basal titration
Titrate insulin
52. Insulin Therapy in Patients with CKD
Diabetic Nephropathy
TIDM: Intensive insulin therapy was more effective as
regards glycaemic control (HbA1c 7.2 vs. 9.1%) than
conventional insulin therapy in 1441 type 1 diabetics treated
for an average treatment period of 6.5 years.
39% reduction in microalbuminuria risk (>40 mg/day)
(primary prevention)
54% reduction in progression to macroalbuminuria
(>300 mg/ day) (secondary intervention)
The effect of intensive treatment of diabetes on thedevelopment and progression of long-term complications
n insulin-dependent diabetes mellitus: The DiabetesControl and Complications Trial ResearchGroup. N Engl J Med 1993; 329:
52
53. Insulin Therapy in Patients with CKD
Diabetic Nephropathy
•T2DMay also benefit from intensive insulin
therapy. In a 6-year study, performed on 110 non-
obese Japanese patients with type 2 diabetes,
intensive insulin therapy was associated with
• primary prevention (7.7 vs. 28%)
• secondary intervention (11.5 vs.32%) .
Ohkubo Y, Kishikawa H, Araki E et al. Intensiveinsulin therapy prevents the progression of diabetic microvascular complications
in Japanese patients withnon-insulin-dependent diabetes mellitus: a randomizedprospective 6-year study. Diabetes Res Clin
Pract1995; 28: 103–117.
53
54. Insulin Therapy in Patients with CKD
Diabetic NephropathyAmong the main limitations of intensive insulin therapy
Hypoglycaemia
Weight gain.
54
55. Insulin Therapy in HD
Diabetic Nephropathy
• In HD patients, insulin requirements are reduced in
probable relationship with an improvement in IR associated to
dialysis procedure
• Hypoglycemic events tended to be higher than in the
predialysis period. Moreover, the residual diuresis decrement
during the first year on HD is associated with a significant
reduction of insulin requirements
• patients with residual diuresis <500 ml/day showed a
reduction in insulin needs by about 29%, whereas no changes
were reported in patients with higher residualDiuresis
55
56. Insulin Therapy in HD
Diabetic Nephropathy
• Adequate glycaemic control in HD diabetic patients : two
doses of intermediate-acting insulin and or one basal insulin +
preprandial dose of rapid-acting insulin as needed .
• HD solutions with high glucose concentration have shown to
be useful in preventing hypoglycemic events during the HD
session, without significant effects on HbA1c
56
60. AGENDA
60
Background of Dysglycemia and CKD
Pathophysiology of Dysglycemia and CKD
Glycemic control and CKD
Insulin therapy and CKD
Conclusions
61. Conclusions
Diabetic Nephropathy Glycaemic control in CKD diabetic patients can be difficult to be
obtained because of multiple factors intrinsic to diabetes, renal
insufficiency and concomitant therapy(pharmacological, dialytic and
immunosuppressive therapy).
IR and hyperinsulinaemia can impair the capacity to reach satisfactory
target blood glucose levels.
Intensive insulin therapy is an adequate option for improving glycemic
control in CKD although it might increase the risk of hypoglycaemic
events.
insulin analogues in CKD patients has been associated with potential
advantages and benefits with regard to glycaemic control.
61