Diabetes,dysglycemia; and chronic kidney disease by prof alaa wafa

Dysglycemia and CKD

BY

Alaa Wafa MD.Associate Professor of internal medicine

Diabetes & Endocrine unit.

Mansoura university

8th international HD course

UNC 15/12/2015

AGENDA

2

Background of Dysglycemia and CKD

Pathophysiology of Dysglycemia and CKD

Glycemic control and CKD

Insulin therapy and CKD

Conclusions

TEAMWORK- the power of a multidisciplinary approach

Patient and

family

Nephrologist

Nurse

Clinician

Diabetes

Educator

Pharmacist

Registered

Dietitian

Social

Work

Diabetes:The Most Common Cause of ESRD

Primary Diagnosis for Patients Who Start Dialysis

Diabetes50.1%

Hypertension27%

Glomerulonephritis

13%

Other

10%

United States Renal Data System. Annual data report. 2000.

No. of patientsProjection95% CI

1984 1988 1992 1996 2000 2004 20080

100

200

300

400

500

600

700

r2=99.8%243,524

281,355

520,240

No

. o

f d

ialy

sis

pati

en

ts

(th

ou

san

ds)

©2006. American College of Physicians. All Rights Reserved.

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.

http://www.worldlifeexpectancy.com/cause-of-death/kidney-disease/by-country/

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

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

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.

Natural History of DN

Comprehensive textbook of Nephrology, 2010

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

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

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

syndromeGlucose

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.

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

HR

for

CV

D m

ort

alit

y (

AC

R s

tudie

s)

ACR, mg/g

Adapted from Matsushita K, van der Velde M, Astor BC, et al. Lancet 2010;375:2073–2081.

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

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

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

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.

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 kidneyA 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

Selected actions of insulin

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.

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


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


23

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

HypertensionOverproduction 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

25

Pathophysiological cardiovascular

consequences of hypoglycaemia

CRP=C-reactive protein; IL-6=interleukin 6; VEGF=vascular endothelial growth factor.

Desouza CV, et al. Diabetes Care. 2010; 33: 1389–1394.

VEGF IL-6 CRP

Neutrophil

activation

Platelet

activation

Factor VII

Blood coagulation

abnormalities

Sympathoadrenal response

Inflammation

Endothelial

dysfunction

Vasodilation

Heart rate variability

Rhythm abnormalities Haemodynamic changes

Adrenaline

Contractility

Oxygen consumption

Heart workload

HYPOGLYCAEMIA

25

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

ConclusionsThe 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%).

• Patients with more variable HbA1c face a higher risk of microvascularcomplications, 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.

• 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.

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

AGENDA

33





Conclusions


-50

-40

-30

-20

-10

0

Diabetes-

related death

Myocardial

infarction

Microvascular

complications

Peripheral

vascular

disease

Lowering HbA1c by 1% significantly reduces:

Reduction in incid

ence r

isk

per

1%

reduction in H

bA

1c

–21%*

–14%*

–37%*

–43%*

*p < 0.0001Stratton IM et al. BMJ 2000;321:405–12

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

Glycaemic Control in Diabetics with CKD

Diabetic Nephropathy

36Diabetes, Obesity and Metabolism, 10,2008 , 811–823

Management of Hyperglycemia in

Type 2 Diabetes, 2015:

A Patient-Centered Approach

Update to a Position Statement of the American Diabetes Association (ADA) and the

European Association for the Study of Diabetes (EASD)

Diabetes Care 2015;38:140–149

Diabetologia 2015;58:429–442

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-i

or

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-RA Mealtime 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%)

Diet modification;

Salt diet reduces blood pressure.

Fibres improves lipid profile.

Phosphorus .

Protein diet .

Dietary modifications

Dietary recommendations depend on the stage of CKD

Sodium <2.4 g/d (< 100 mmol/d)

Protein < 0.8mg/kg /day .

potassium > 4(g/d)

Calcium and magnesium supplements

Phosphorus < 1.7 (g/d).

Exercise and smoking cessation.

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

Antihyperglycemic Agents and CKD

45

AGENDA

46





Conclusions

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.

• 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

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%.



reach FBG target.




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,


• Start: 4U, 0.1 U/kg, or 10% basal dose. If A1c<8%, consider ê basal by same amount.



• 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.





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.






reach FBG target.




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,


If not controlled,


• Start: 4U, 0.1 U/kg, or 10% basal dose. If A1c<8%, consider ê basal by same amount.



• 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.





Lifestyle changes plus metformin (± other agents)

BasalAdd basal insulin

Basal PlusAdd prandial insulin at main meal

Basal BolusAdd 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 titrationTitrate insulin

Insulin Therapy in Patients with CKD

Diabetic NephropathyTIDM: 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:

977–986.

52



•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


Diabetic NephropathyAmong the main limitations of intensive insulin therapy

Hypoglycaemia

Weight gain.

54

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

Insulin Therapy in HD


• 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

Insulin Therapy in PD


57

Insulin Analogues in Renal Insufficiency


58

AGENDA

60





Conclusions

Conclusions

Diabetic NephropathyGlycaemic 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

[email protected]@mans.edu.eg

Thank

you

mailto:[email protected]

Health & Medicine

Diabetes,dysglycemia; and chronic kidney disease by prof alaa wafa