1. Management of Diabetes in Patients with Impaired Kidney Function
RAK Nephrology Conference
Management of Diabetes in Patients with Impaired Kidney Function
Salem A Beshyah, PhD FRCP FACP FACE
Consultant Endocrinologist
Centre for Diabetes and Endocrinology
Sheikh Khalifa Medical City
Abu Dhabi, U.AE.

2. Management of Diabetes in Patients with Impaired Kidney Function
Disclaimer This slide set provided here is exactly as used by the speaker on Health Care Professionals are welcome to Download, amend, update and use as they deem appropriates and on their responsibility.

3. Management of Diabetes in Patients with Impaired Kidney Function
Disclosure The speaker has NO conflicts of interests related to this presentation

4. At the end of the presentation, the audience be able to:
Management of Diabetes in Patients with Impaired Kidney Function: Learning Objectives
At the end of the presentation, the audience be able to:
Recall the role of the kidney in glucose metabolism.
Recognize the effects of CKD on diabetes control and pharmacokinetics of anti-diabetic drugs
Review the management of glycaemia effectively in patients with declining kidney function.

5. Management of Diabetes in Patients with Impaired Kidney Function: Agenda
RECAP: The role of the kidneys in carbohydrate metabolism and insulin handling and the changes in carbohydrate metabolism in CKD
IN PRACTICE: Management of Diabetes in CKD:
Management diabetes in CKD.
Effective and safe use of anti-diabetic agents.
Special Issues : Monitoring
TAKE HOME MESSAGE: Summary and Conclusions.

6. Glucose Homeostasis in the Fasting State Illustrated by the glucose production and utilization post-absorptive State 5
1.5
8.0
10 umol/kg/min
0.5
Glucose enters the circulation when fasting, by hepatic glucose efflux. This is initially derived from glycogen stores and then predominantly via gluconeogenesis from certain amino acids, such as alanine, and carbohydrate substrates, such as glycerol and lactate. Although the kidney is capable of gluconeogenesis, insufficient glucose is produced to affect plasma glucose concentrations. The liver thus has a predominant role in regulating the plasma glucose concentration. The liver is unable to produce normal glucose efflux in the absence of cortisol or growth hormone, and the presence of glucagon may be even more important. A protein meal stimulates glucagon as well as insulin secretion, and the glucagon probably prevents insulin-induced hypoglycaemia that would occur if protein were not accompanied by carbohydrate. The role of glucagon is apparent from a somatostatin infusion in man, that inhibits both insulin and glucagon production and induces hypoglycaemia. Fasting plasma glucagon concentrations increase in response to hypoglycaemia and other stresses in man, as do those of cortisol, growth hormone, and adrenaline. The plasma glucagon rise after birth may be particularly important in preventing neonatal hypoglycaemia, and its lack may contribute to the neonatal hypoglycaemia sometimes found in infants of diabetic mothers.
Insulin is the major hormone regulating fuel supply and is the only known physiological hormone to directly lower the plasma glucose. Other insulin-like peptides are present in plasma, and their biological activity in vitro on muscle or adipose tissues is not completely abolished by addition of insulin antiserum. This remaining activity is termed non-suppressible insulin-like activity (NSILA). These peptides are growth promoting and, when assayed in vitro, they were termed somatomedins. There are two major fractions, an ethanol-precipitated protein (NSILA-p) and soluble fraction (NSILA-s). The NSILA-s has been purified and consists of pro-insulin-related peptides, called insulin-like growth factors, ILGF-I and ILGF-II. ILGF-I is primarily produced by the liver and is stimulated by growth hormone production. Control of ILGF-II secretion is less well defined. The peptides are thought to be primarily growth factors rather than being concerned with fuel supply. In plasma both ILGF-I and ILGF-II are bound to specific binding proteins.
2.0
2.0
0.5

7. Glomerular Filtration (60%)
Insulin Metabolism
Peri-tubular Uptake
(40%)
3/4
1/4
Circulation
Glomerular Filtration (60%)
Rabkin R et al. The renal metabolism of insulin. Diabetologia 1984; 27: . 7 7

8. Intra-renal Pathways of Insulin Removal
Filtrered insulin is internalized by by endocytosis and thereafter degraded into amino acids into the peritubular vessls. Insulin removed from postglomerular peritubular vessels binds to the contraluminal cell membrave. This process in both receptor and non-recepror mediated. (Adapted from Rabkin R et al. The renal metabolism of insulin. Diabetoligia 1984;
27: )
Rabkin R et al. The renal metabolism of insulin. Diabetologia 1984; 27: 8

9. Renal Handling of Insulin
The renal clearance of insulin is 200 ml/min (due to the contribution of tubular secretion).
6-8 units of insulin are degraded by the kidney/day (25% of the daily endogenous insulin production).
Renal metabolism is enhanced in DM on exogenous insulin. (injected insulin enters the systemic circulation directly without first passing through the liver).

10. The kidney plays a role in carbohydrate metabolism by:
The Role of the Kidneys in Carbohydrate Metabolism in Health and Disease I. Pathophysiology
The kidney plays a role in carbohydrate metabolism by:
Glucose is filtered and reabsorbed
Insulin disposal
Disposal of most antidiabetic drugs
Significant contribution to basal (fasting) glucose level by 20-25%
The kidney is a target organ for damage by macro and microvascular diabetic complications.
The kidney is now a target for Treatment.

11. In DM+CKD, insulin requirements show a biphasic course:
The Role of the Kidneys in Carbohydrate Metabolism in Health and Disease II. Clinical Implications.
In DM+CKD, insulin requirements show a biphasic course:
A. As renal function deteriorates in both DM types: Glucose control commonly deteriorates (insulin resistance)
B. In ESRD; the fall in insulin clearance results in improvement in glucose tolerance judged by:
Lower insulin requirements
Lower OHA dose
cessation of insulin therapy
Spontaneous hypoglycemia (multi-factorial).

12. Management of Diabetes in Patients with Impaired Kidney Function: Agenda
The role of the kidneys in carbohydrate metabolism and insulin handling and the changes in carbohydrate metabolism in CKD 
Management of Diabetes in CKD:
Management diabetes in CKD. 
Effective and safe use of anti-diabetic agents.
Special Issues : Dialysis, Monitoring, Targets…
Summary and Conclusions.

13. Management of Diabetes in Chronic Kidney Disease: The Challenges
Higher levels of HbA1c were associated with higher death rates in patients with DM and CKD after adjusting for markers of inflammation and malnutrition.
ESRD significantly alters:
glycemic control
results of hemoglobin A1c testing
the excretion of anti-diabetic medications.
Various and opposing effects of ESRD and dialysis can make BG levels fluctuate widely, placing patients at risk of hypoglycemia and present a challenge for physicians.

14. Management of Glycemia in Chronic Kidney Disease: Context – Scarce Data

15. Management of Glycemia in Chronic Kidney Disease: Context
Management of Glycemia in Chronic Kidney Disease: Context. Sources for in depth discussion

16. Glycemia-Related Issues in CKD
Glucose metabolism & pharmacokinetics
Increased risk of hyperglycemia
Increased production and use of glucose
Impaired glucose disposal
Increased insulin resistance
Increased risk of hypoglycemia
Impaired renal gluconeogenesis
Decreased insulin clearance
Decreased clearance of oral hypoglycemic agents
Monitoring of Glycemic Control
Falsely increased HbA1c
carbamylated hemoglobin in erythrocytes interfering with HbA1c assay
Falsely decreased HbA1c
Increased RBC turnover (reduced life span)
Use of erythropoietin

17. Kidney Disease Factors:
Factors Influencing Management Strategy of Glycaemia in Chronic Kidney Disease
Kidney Disease Factors:
Severity of kidney disease
Anemia
Haemolysis
Dialysis and type
Diabetes Factors:
Type of diabetes
Severity
Previous treatment
Hypoglycaemia (+/- unawareness)
General Factors:
Age
Expected survival
Resource availability.
Cost
Family/professional support
Patient Choice:
Ability to manage
Willingness to manage

18. Management of Diabetes in Patients with Impaired Kidney Function: Agenda
The role of the kidneys in carbohydrate metabolism and insulin handling and The changes in carbohydrate metabolism in CKD
Management of Diabetes in CKD:
Management diabetes in CKD. 
Effective and safe use of anti-diabetic agents. 
Special Issues : Monitoring
Summary and Conclusions.
Introduction:
Diabetic nephropathy is the most common cause for end-stage renal disease (ESRD). Chronic renal failure is associated with miscellahous alterations in carbohydrate and insulin
metabolism.. Moreover, several specific therapies employed in renal insufficiency also influence pharmacological therapy of diabetes in uraemic patients.. In patients with altered renal function, therapeutic possibilities are limited due to the accumulatin of some
oral agents and/or their metabolites at the reduced glomerular filtration rate (GFR). The connection between kidney and insulin metabolism is well known for many years (Horton
et al, 1968). For insulin metabolism the kidneys are one of its target organs. Chronic renal failure is associated to multiple alterations in the carbohydrate and insulin metabolism that
should be taken into account when treating diabetic patients with altered renal function (DeFronzo et al, 1973). Specific therapeutic needs (oral agents or insulin) will be determined
based on the degree of insulin resistance or insulin deficiency of patients with renal insufficiency (Rabkin e al,1984). A good metabolic control is not only important in the early
phase of diabetic nephropathy but also in diabetic patients with ESRD. It was shown in several studies, that metabolic control under antidiabetic therapy is a predictor for
prognosis of patents with renal replacement therapy (Morokia et al, 2001). A good glycemic control can reduce the progression of atherosclerosis (Oomichi et al, 2006) and improve the
survival in patients treated with hemodialysis (Kovesdy et al, 2008). Though, in a recent study it was suggested that aggressive glycemic control cannot be routinely recommended
for all diabetic hemodialysis patients on the basis of reducing mortality risk (Williams et al 2010). The majority of uremic type 2-diabetic patients need insulin, however, a smaller part
of these diabetic patients can also be treated with oral antidiabetic agents. The problem of the topic of this study is the fact, that there are only few data in the literature
concerning antidiabetic therapy in type 2 diabetic patients with ESRD (Biesenbach et al, 2010).

19. Current and new antidiabetic medications: benefits and risks
Intervention
Advantages
Disadvantages
Metformin
Weight neutral
May improve lipid profile
GI side effects, Lactic acidosis (rare)
Sulphonylureas
Well established
Weight gain, Hypoglycaemia
Thiazolidinediones
Durable glycaemic control
Fluid retention, congestive heart failure
Weight gain, bone fractures
Meglitinides
Short duration
Weight gain, Frequent dosing
Insulin
No dose limit
Improves lipid profile
Injections, Weight gain, Hypoglycaemia
-Glucosidase inhibitors
Do not cause hypoglycaemia
Frequent GI side effects
Dosing 3 times/day
Amylin analogues
Weight loss
Injections, frequent GI side effects
DPP-4 inhibitors
GLP-1 agonists
SGLT2 inhibitors
Insulin-independent, weight reduction, BPlowering
eGFR dependent, mycotic infection, risk of dehydration
Biguanide (metformin) has additional clinical benefits such as weight stabilisation/reduction, reduction in hypertriglyceridaemia, lowering plasma fatty acids and HDL cholesterol. Common adverse events include abdominal discomfort and other gastrointestinal adverse effects. The most serious adverse event associated with metformin is lactic acidosis; although rare, the mortality rate is high.1
Sulphonylureas (e.g. glimepiride, glipizide) have been extensively used for the treatment of type 2 diabetes for nearly 50 years. Hypoglycaemia is the most common adverse effect of sulphonylurea therapy. Weight gain is regarded as a class effect of sulphonylurea therapy, typically amounting to 1–4kg and stabilising after approximately 6 months.
Thiazolidinediones (e.g. pioglitazone, rosiglitazone) improve whole-body insulin sensitivity via multiple actions on gene regulation. Thiazolidinediones are associated with fluid retention with increased plasma volume, a reduced haematocrit and a decrease in haemoglobin concentration.1
Meglitinides (e.g. nateglinide, repaglinide) have a rapid onset of action and a short duration of hypoglycaemic effect which make them suitable for pre-prandial administration. A small increase in bodyweight can be expected in patients.
Among insulin therapies (e.g. insulin aspart, insulin glulisine), options include rapid-acting, intermediate-acting, and long-acting human insulin preparations. Weight gain and hypoglycaemia are associated with insulin therapy.2
-glucosidase inhibitors (e.g. acarbose, miglitol) do not cause weight gain, can reduce post-prandial hyperinsulinaemia and have lowered plasma triglyceride concentrations in some studies. Their use has been limited by adverse gastrointestinal effects.1
Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. Nausea is the most common side effect.3
DPP-4 inhibitors (e.g. sitagliptin, vildagliptin) are generally well tolerated and weight neutral. Long-term data on cardiovascular outcomes and safety are needed.4
GLP-1 agonists (e.g. exenatide, liraglutide) have shown a favourable effect on weight, are not associated with hypoglycaemia, but common side effects include gastrointestinal disturbances.4
Krentz A and Bailey C. Drugs 2005;65:385–411.
Carver C. Diabetes Educ 2006;32:910–917.
Krentz A, et al. Drugs 2008;68:2131–2162.
Bosi E, et al. Diabetes Res Clin Pract 2008;82:S102–S107. 19 19

20. Fluctuation of blood glucose and monitoring of glycemic control in CKD
Several factors can negatively influence glycaemic control in diabetic patients:
poor food intake
insufficient exercise
uraemia-induced anorexia
insulin metabolismdisorders
insulin resistance
and reduced insulin clearance
inadequate drug therapy.
In diabetic patients with ESRD additional factors can cause blood glucose (BG) fluctuations.

21. Relationship among therapeutic class, medication dose and creatinine clearance I. Metformin
Risks: Lactic acidosis, marked GI side effects.
USA prescribing information:
contraindication for men with serum creatinine X1.5 mg/dL and women with serum creatinine X1.4 mg/dL
UK guideline allows metformin in patients with eGFR >30
KDIGO: metformin in patients with eGFR >45
eGFR = mL/min/1.73 m2
Betonico CC et al. CLINICS 2016;71(1):47-53

22. First generation are mostly renaly excreted - contraindicated
Relationship among therapeutic class, medication dose and creatinine clearance II. Sulphonylureas
First generation are mostly renaly excreted - contraindicated
Second Generation: partly metabolized by the liver, may be used cautiously.
Third generation: best options with monitoring for hypoglycemia 

23. Relationship among therapeutic class, medication dose and creatinine clearance II. Sulphonylureas
Gliclazide
Reduce dose if eGFR <30
Not recommended if eGFR <15
Glimepiride:
Initiate conservatively at 1 mg daily
Avoid use if eGFR <60
Glipizide:
No dose adjustment required
Glibenclamide
Avoid use in patients with eGFR <60   
eGFR in terms = mL/min/1.73 m2
Betonico CC et al. CLINICS 2016;71(1):47-53

24. Relationship among therapeutic class, medication dose and creatinine clearance III. DPP-4 inhibitors
Sitagliptin and saxagliptin: dose adjustment required
Sitagliptin
50 mg daily if eGFR 30–50
25 mg daily if eGFR <30
Saxagliptin: 2.5 mg daily if eGFR <50
Alogliptin:
1.25 mg/day when eGFR 30–60
<0.625 mg/day eGFR <30 (or on hemodialysis)
Linagliptin No dose adjustment required 
eGFR in terms = mL/min/1.73 m2
Betonico CC et al. CLINICS 2016;71(1):47-53

25. Relationship among therapeutic class, medication dose and creatinine clearance IV. Meglitinides, AGI’s and TZD’s
Repaglinide:
Initial dose of 0.5 mg before meals when eGFR <30
Nateglinide (not used in UAE):
Caution when used with eGFR <30
Initiate with 60 mg before meals
a-Glucosidase inhibitors:
Only Acarbose is available in UAE.
Avoid if eGFR <30
TZDs (Pioglitazone only)
No dose adjustment required.
Caution in CKD & hypervolemia
Betonico CC et al. CLINICS 2016;71(1):47-53

26. Relationship among therapeutic class, medication dose and creatinine clearance V. GLP-1 RA
Liraglutide ( mg daily)
No restrictions if eGFR >30
Dulaglutide ( mg weekly)
No dose modifications on any renal impairment.
Exenatide: (QD= 5-10 mcg; QW = 2 mg)
eGFR 30 and 50: Dose <5 mcg daily.
eGFR <30: QDE -Avoid QDE; DWE -Use with caution
Lixisenatide (10,20 mcg)
Avoid if eGFR <50.  

27. Relationship among therapeutic class, medication dose and creatinine clearance VI. SGLT2 inhibitors
Canagliflozin: (100,300)
eGFR >60: No dose adjustment required.
100 mg daily if eGFR 45–59.
Empagliflozin: (10,25)
GFR ≥45: No dosage adjustment required
eGFR <45: Do not initiate
Discontinue if eGFR persistently falls below 45
Dapagliflozin: (5,10)
eGFR: <60 Avoid use.
Discontinue use if eGFR <45 (?60)

28. Relationship among therapeutic class, medication dose and creatinine clearance VI. SGLT2 inhibitors
Mild eGFR reduction may occure after initiation of SGLT2 inhibitors.
However:
Long term slowing of renal disease progression has been documented with the first trial (Empa-reg).
Perhaps
for now: Caution if reduction in eGFR
Marked
Progressive
Persistent

29. Relationship among therapeutic class, medication dose and creatinine clearance VII. Insulin
Consider insulins as:
Short/Rapid
Intermeditae
Long or Basal
Analogues have less risk of hypoglycaemia
Premix insulin may be used within the context of meal pattern
Adjust insulin doses as follows:
Based on regular SMBG
If established on insulin:
Reduce by 25% - GFR<50
Reduce by 50% - GFR<10
Adjust for changing Mode of dialysis
O’Toole et al. 2012

30. Oral Anti-diabetic Agents in Dialysis- Summary
Group (Examples)
Adverse effects in CKD
Use during dialysis
Sulfonylurea (LA)
Hypoglycemia,
Do not use
Sulfonylurea (SA)
Hypoglycemia, weight gain
Use carefully
Biguanide (Metformin)
Risk of lactic acidosis (GFR<20 ml/min)
Thiazolidinedione (Pioglitazone)
Anemia and edema, CHF
Mitiglinide (Repaglinide)
SGLT 2 inhibitors
Not effect
Do Not use

31. Diabetes in the Dialysis Patient: The Principles
Poor control is associated with extensive morbidity and mortality.
Capillary BG measurements can be overestimated in peritoneal dialysis patients using icodextrin, leading to risk of ‘missed’ hypoglycaemic episodes.
Interpretation of HbA1c in dialysis populations is complicated.
The therapeutic arsenal to achieve glycaemic control is severely restricted in patients with ESRD.
Management of DM complications centres around risk reduction, early identification, good glycaemic control and a multidisciplinary team

32. Recommended Diabetes Control Targets in Dialysis Patients
Professional Body
HbA1c Target
The Renal Association, 2011
7.5%
Joint British Societies, 2005
6.5%
The National Institute for Health and Clinical Excellence (NICE, UK), 2011
% (individuallize)

33. Proposed Management of Diabetes in CKD by Stage of Renal Function
Description
GFR ml/min
HbA1c %
Drug regimens I
CKD with normal or mildly decreased GFR 90
<7.0
Standard II
CKD with mildly decreased GFR
60-90
III
Moderately CKD
30-59
a. Discontinue metformin, most SU’s, Nateglinide, Glucosidae inhibitors,
GLP-1 analogs,
b. Review DDP-IV Inhibitors. IV
Severe CKD
15-29
Insulin – adjusted dose V
ESRD or Dialysis
<15 or RR
Seaquist and Ibrahim, JCEM 2010

34. Measures of Glycaemic Control in Patients on Various Therapeutic Modalities at the Start and after 12 Months of Haemodialysis
Variable
Start
12 Months
Change (%)
HbA1c (%)
Diet
7.4±0.8
7.1±0.6
-4% SU
7.6±1.3
7.4±1.2
+1%
Insulin
7.9±1.1
7.7±0.8
-2%
Hypoglycemia (n/patient/month):
0.4
0.6
+50%
0.9
1.1
+83%
Biesenbach et al, 2010).

35. Management of Diabetes in Peritoneal Dialysis

36. Diabetologist must keep up to date with the dialysis practices…
Diabetologist must keep up to date with the dialysis practices….to be able to adjust the insulin regimens appropriately.

37. Diabetes Management in Peritoneal Dialysis I
The evidence for improving glycemic control in patients on dialysis having an impact on mortality or morbidity is sparse.
Improving glycaemic control in patients on dialysis is very challenging
difficulties with hypoglycemic drugs
monitoring difficulties
dialysis strategies that exacerbate hyperglycemia or hypoglycemia
Therapeutic nihilism or inertia.

38. Diabetes Management in Peritoneal Dialysis II
Standard drug therapy for hyperglycemia is clearly not possible in patients on dialysis.
Sulphonylureas and insulin are the mainstay of treatment.
Newer therapies for hyperglycaemia have become available, but until recently, renal failure has precluded their use.
Newer gliptins, however, are now licensed for use in ‘severe renal failure’. They have yet to be trialled in dialysis patients.
Diabetic patients on dialysis have special needs, as they have a much greater burden of complications (cardiac, retinal and foot)

39. Diabetes Management in Peritoneal Dialysis III
They may be best managed in a multidisciplinary diabetic–renal clinic setting, using the skills of:
diabetologists
nephrologists.
clinical nurse specialists in nephrology and diabetes.
Dietitians.
podiatrists.

40. Intra-peritoneal insulin in peritoneal dialysis patients
PROS
More physiologic absorption (less fluctuation of BG).
Continuous insulin infusion.
Avoids injections
Less hyper-insulinemia
Avoids antibody formation.
Improved HbA1c
CONS
High insulin doses
Higher cost
Insulin losses in effluent
Lipid effects
Specific dialysis complications: e.g. excess glucose absorption.
Insulin in peritoneal dialysis
The fluctuations of blood glucose, hyperinsulinemia and the rare formation of insulin antibodies under subcutaneous insulin (sc) injection can be prevented by peritoneal dialysis PD). Investigations of insulin in patients treated with PD indicate that the intraperitoneal (ip) administration on of insulin leads to more even glucose levels, but that when dialysis fluids with glucose concentrations higher than 13.6 g/L are used, the absorption of glucose from the abdominal cavity is greater in PD with ip insulin treatment than it is with sc administration (Quellhorst, 2002) The raised glucose absorption from the abdominal cavity in ip insulin administration must be regarded as a disadvantage. Investigations of insulin in PD showed, that after a dwell time of 30 min, the absorption of insulin from the abdominal cavity in the patients with diabetes was much higher than in the patients without diabetes. In several studies the authors compared both routes of insulin administration. they observed a better fall of HbA1c after switching from sc to ip administration (Grodstein et al, 1981)
(Quellhorst, 2002; Grodstein et al, 1981)

41. Lack of a Relationship of Risk of Vascular Disease to Anti-diabetic Therapy
CVD=Cerebro-vascular disease.
CAD= Coronary artery disease.
PAD=peripheral artery disease.
Anti-diabetic therapy:
diet alone (10)
Sulphonylureas (12)
Insulin (42)

42. Management of Diabetes in Patients with Impaired Kidney Function: Agenda
The role of the kidneys in carbohydrate metabolism and insulin handling and The changes in carbohydrate metabolism in CKD
Management of Diabetes in CKD:
Management diabetes in CKD. 
Effective and safe use of anti-diabetic agents. 
Special Issues : Monitoring 
Summary and Conclusions.

43. Monitoring of Glycemic Control I
Real time:
SMBG
CGM
FGM
Long term:
HbA1c
Fructosamine
Glycated
It is well known that hemoglobin A(1c) is no exact parameter for glycemic control in uremic diabetic patients (Joy et al , 2002). Especially, the hemoglobin A(1c) level can be falsely high in ESRD, but it is still a reasonable measure of glycemic control in this population. The cause of the falsely evated level in diabetic patients with ESRD is the elevated blood urea nitrogen,which causes formation of carbamylated hemoglobin, which is indistinguishable from glycosylated hemoglobin. Other factors such as the shorter red life span of red blood cells, iron deficiency, recent transfusion, and use of erythropoietin-stimulating agents may also cause underestimation of glucose control. In a recent study it was reported that glycated albumin is a better glycemic indicator than glycated hemoglobon values in hemodialysis patientswith diabetes (Inaba, eet al, 2007) However, in the clinical practise glycated hemoglobin was not replaced by glycated albumin or fructosamine

44. Monitoring of Glycemic Control II. HbA1c
HbA1c level can be falsely high in ESRD, but it is still a reasonable measure of control. (Joy et al , 2002).
It may be falsely elevated due to high BUN producing a compound indistinguishable from HbA1c.
Other factors:
Life span of RBC
iron deficiency
transfusions
erythropoietin-stimulating agents.
It is well known that hemoglobin A(1c) is no exact parameter for glycemic control in uremic diabetic patients (Joy et al , 2002). Especially, the hemoglobin A(1c) level can be falsely high in ESRD, but it is still a reasonable measure of glycemic control in this population. The cause of the falsely evated level in diabetic patients with ESRD is the elevated blood urea nitrogen,which causes formation of carbamylated hemoglobin, which is indistinguishable from glycosylated hemoglobin. Other factors such as the shorter red life span of red blood cells, iron deficiency, recent transfusion, and use of erythropoietin-stimulating agents may also cause underestimation of glucose control. In a recent study it was reported that glycated albumin is a better glycemic indicator than glycated hemoglobon values in hemodialysis patientswith diabetes (Inaba, eet al, 2007) However, in the clinical practise glycated hemoglobin was not replaced by glycated albumin or fructosamine

45. Monitoring of Glycemic Control III. Alternatives
Fructosamine: short term
Glycated albumin may be a better indicator than HbA1c in hemodialysis patients with diabetes
(Inaba, et al, 2007.
No change in the clinical practice.
It is well known that hemoglobin A(1c) is no exact parameter for glycemic control in uremic diabetic patients (Joy et al , 2002). Especially, the hemoglobin A(1c) level can be falsely high in ESRD, but it is still a reasonable measure of glycemic control in this population. The cause of the falsely evated level in diabetic patients with ESRD is the elevated blood urea nitrogen,which causes formation of carbamylated hemoglobin, which is indistinguishable from glycosylated hemoglobin. Other factors such as the shorter red life span of red blood cells, iron deficiency, recent transfusion, and use of erythropoietin-stimulating agents may also cause underestimation of glucose control. In a recent study it was reported that glycated albumin is a better glycemic indicator than glycated hemoglobon values in hemodialysis patientswith diabetes (Inaba, eet al, 2007) However, in the clinical practise glycated hemoglobin was not replaced by glycated albumin or fructosamine

46. Management of Diabetes in Patients with Impaired Kidney Function: Agenda
The role of the kidneys in carbohydrate metabolism and insulin handling and The changes in carbohydrate metabolism in CKD
Management of Diabetes in CKD:
Management diabetes in CKD. 
Effective and safe use of anti-diabetic agents. 
Special Issues : Dialysis, Monitoring , Targets 
Summary and Conclusions. 

47. Management of Diabetes in Chronic Kidney Disease: Summary I
Management of Diabetes in Chronic Kidney Disease: Summary I. Principles and Orals
Glycemic control and monitoring in ESRD are complex.
Patients with ESRD are especially susceptible to hypoglycemia, special caution with medication is waranted.
ESRD patients need ongoing diabetes education, with an emphasis on how to recognize and treat hypoglycemia.
Diabetic pharmacotherapy in ESRD should be individualized:
Targets hemoglobin A1c value (7%)
FBG <140 mg/dL
Postprandial glucose <200 mg/dL.
Rationale chice of oral antidiabetic drugs
Glitazones may cause fluid overload.
SGLT2-inhibitors may play a role down to eGFR 30

48. Management of Diabetes in Chronic Kidney Disease: Summary II
Management of Diabetes in Chronic Kidney Disease: Summary II. Injectables and Organization
Safety of some GLP-1 RA has been established.
Basal insulin with bolus insulin is the most effective insulin regimen? Acceptability?
Analogues are favorable than Isophane and regular insulin.
Patients may prefer convenience of a premixed insulin. Analogues=less hypo’s
ESRD with T1DM, dose of insulin therapy may be half the dose in patients without renal failure.
ESRD with T2DM, insulin therapy should be started at a low dose …. Calculate versus empirical.
Individualized adjustment by SMBG patterns.
Find an endocrinologist with expertise in managing diabetes in ESRD if problems. Ideally joint care.

49. Management of Diabetes in Chronic Kidney Disease: Take Home Message
In CKD, blood glucose can fluctuate due to various and opposing effects of ESRD and dialysis.
HbA1c can be falsely high in ESRD, but it remains the most reasonable measure of control.
Most diabetes drugs are excreted at least in part by the kidney; ESRD patients are at greater risk of hypoglycemia.
Many OHA are either contraindicated or not recommended in ESRD.
Insulin doses should be lowered in those with low GFR.
Local collaboration & protocols are advisable.