diabetes & ramadan (2)
TRANSCRIPT
ALAA WAFA. MDAssociate Professor of Internal Medicine
PGDIP DM Cardiff University UKDiabetes and Endocrine unit
Mansoura university
Diabetes Dilemma
Blood glucose
Insulin and Glucagon Regulate Normal Glucose Homeostasis
Glucose output Glucose uptake
Glucagon (α cell)
Insulin(β cell)
Pancreas
Liver
Muscle
Adipose tissue
Fasting state Fed state
Porte D Jr, Kahn SE. Clin Invest Med. 1995;18:247–254.Adapted with permission from Kahn CR, Saltiel AR. In: Kahn CR et al, eds. Joslin’s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:145–168. 4
Islet dysfunction
Adapted from Buse JB et al. In Williams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003:1427–1483; Buchanan TA Clin Ther 2003;25(suppl B):B32–B46; Powers AC. In: Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill, 2005:2152–2180; Rhodes CJ Science 2005;307:380–384.
The Pathophysiology of Type 2 Diabetes Includes Multiple Defects
Pancreas
Insulin deficiency
LiverMuscle & Fat
Excess glucagon Diminished
insulin
Diminished
insulin
Beta cellproduces less insulin
Alpha cellproduces excess glucagon
Insulin resistance (decreased glucose
uptake)Excess Glucose
Output
HYPERGLYCEMIA
Time
Pancreatic Islet Cells in Type 2 Diabetes
B cells
α cells
B cells
α cells
The Core Defects in type 2 diabetes:
Insulin resistance in
peripheral tissues
Excess Hepatic Glucose Production due to
1)increased glucagon2)insulin insufficiency3)insulin resistance
Insulin deficiency due to insufficient pancreatic insulin
release
Reprinted from Primary Care, 26, Ramlo-Halsted BA, Edelman SV, The natural history of type 2 diabetes. Implications for clinical practice, 771–789, © 1999, with permission from Elsevier.
Development and Progression of Type 2 Diabetes and Related Complications*
*Conceptual representation.
Insulin level
Insulin resistance
Hepatic glucose production
Postprandial glucose
Fasting plasma glucose
Beta-cell function
Progression of Type 2 Diabetes Mellitus
Impaired Glucose Tolerance
Diabetes Diagnosis
Frank Diabetes
4–7 years
Development of Macrovascular ComplicationsDevelopment of Microvascular Complications
Type 2 diabetes is a progressive disease8
Conceptual representation adapted from Ramlo-Halsted BA, Edelman SV. Prim Care 1999;26(4):771–789. © 1999 Elsevier
Insulin level
Insulin resistance
Hepatic glucose production
Postprandial glucose
Fasting plasma glucose
Beta-cell function
Progression of Type 2 Diabetes
Impaired Glucose Tolerance
Diabetes Diagnosis
Diabetes
4–7 years
Development of Macrovascular ComplicationsDevelopment of Microvascular Complications
New era of treatment of T2DM
peripheralglucose uptake hepatic
glucose production
pancreatic insulinsecretion
pancreatic glucagonsecretion
gutcarbohydratedelivery &absorption
incretineffect
HYPERGLYCEMIA?
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Multiple, Complex Pathophysiological Abnormalities in T2DM
_
_
+renal glucose excretion
peripheralglucose uptake hepatic
glucose production
pancreatic insulinsecretion
pancreatic glucagonsecretion
gutcarbohydratedelivery &absorption
incretineffect
HYPERGLYCEMIA?
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Multiple, Complex Pathophysiological Abnormalities in T2DM
_
_
+renal glucose excretion
DA agonists
T Z D sMetformin
S U sGlinides
DPP-4 inhibitors
GLP-1Ragonists
A G I s
Amylinmimetics
Insulin
Bile acidsequestrants
Lifestyle Changes
Adapted from Riddle MC. Endocrinol Metab Clin North Am. 2005;34:77–98.
Diet and Exercise
Oral Monotherapy
Standard Approach to the Management of T2DM: Treatment Intensification
Oral Combination +
+Oral + InjectableIncretin Mimetics
Oral + Insulin + +
Insulin
Management of Hyperglycemia in Type 2 Diabetes, 2015:
A Patient-Centered ApproachUpdate to a Position Statement of the American Diabetes Association (ADA)
and the European Association for the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149Diabetologia 2015;58:429–442
Glycemic targets
- HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l])
- Pre-prandial PG <130 mg/dl (7.2 mmol/l)
- Post-prandial PG <180 mg/dl (10.0 mmol/l)
- Individualization is key: Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0%+) - older, comorbidities,
hypoglycemia prone, etc.
- Avoidance of hypoglycemia
PG = plasma glucose
ADA-EASD Position Statement Update: Management of Hyperglycemia in T2DM, 2015
Diabetes Care 2012;35:1364–1379; Diabetologia 2012;55:1577–1596Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 1. Modulation of the intensiveness of glucose lowering therapy in T2DM
Oral Class Mechanism Advantages Disadvantages CostBiguanides • Activates AMP-
kinase (?other)• Hepatic glucose production
• Extensive experience• No hypoglycemia• Weight neutral• ? CVD
• Gastrointestinal• Lactic acidosis (rare)• B-12 deficiency• Contraindications
Low
Sulfonylureas • Closes KATP channels• Insulin secretion
• Extensive experience• Microvascular risk
• Hypoglycemia• Weight • Low durability• ? Blunts ischemic preconditioning
Low
Meglitinides • Closes KATP channels• Insulin secretion
• Postprandial glucose• Dosing flexibility
• Hypoglycemia• Weight • ? Blunts ischemic preconditioning• Dosing frequency
Mod.
TZDs • PPAR-g activator• Insulin sensitivity
• No hypoglycemia• Durability• TGs (pio)• HDL-C • ? CVD events (pio)
• Weight • Edema/heart failure• Bone fractures• LDL-C (rosi)• ? MI (rosi)
Low
Table 1. Properties of anti-hyperglycemic agents Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0
Oral Class Mechanism Advantages Disadvantages Costa-Glucosidase inhibitors
• Inhibits a-glucosidase• Slows carbohydrate digestion / absorption
• No hypoglycemia• Nonsystemic• Postprandial glucose• ? CVD events
• Gastrointestinal• Dosing frequency• Modest A1c
Mod.
DPP-4inhibitors
• Inhibits DPP-4• Increases incretin (GLP-1, GIP) levels
• No hypoglycemia• Well tolerated
• Angioedema / urticaria• ? Pancreatitis• ? Heart failure
High
Bile acid sequestrants
• Bind bile acids• ? Hepatic glucose production
• No hypoglycemia• LDL-C
• Gastrointestinal• Modest A1c• Dosing frequency
High
Dopamine-2agonists
• Activates DA receptor• Alters hypothalamic control of metabolism• insulin sensitivity
• No hypoglyemia• ? CVD events
• Modest A1c• Dizziness, fatigue• Nausea• Rhinitis
High
SGLT2 inhibitors
• Inhibits SGLT2 in proximal nephron• Increases glucosuria
• Weight• No hypoglycemia• BP• Effective at all stages
• GU infections• Polyuria• Volume depletion• LDL-C• Cr (transient)
High
Table 1. Properties of anti-hyperglycemic agents Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0
Injectable
Class
Mechanism Advantages Disadvantages Cost
Amylin mimetics
• Activates amylin receptor• glucagon• gastric emptying• satiety
• Weight• Postprandial glucose
• Gastrointestinal• Modest A1c • Injectable• Hypo if insulin dose not reduced• Dosing frequency• Training requirements
High
GLP-1 receptor agonists
• Activates GLP-1 R• Insulin, glucagon• gastric emptying• satiety
• Weight• No hypoglycemia• Postprandial glucose• Some CV risk factors
• Gastrointestinal• ? Pancreatitis• Heart rate• Medullary ca (rodents)• Injectable• Training requirements
High
Insulin • Activates insulin receptor• Myriad
• Universally effective• Unlimited efficacy• Microvascular risk
• Hypoglycemia• Weight gain• ? Mitogenicity• Injectable• Patient reluctance• Training requirements
Variable
Table 1. Properties of anti-hyperglycemic agents Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0
Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
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%)
Figure 3. Approach to starting & adjusting insulin in T2DM
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 3. Approach to starting & adjusting insulin in T2DM
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Figure 3. Approach to starting & adjusting insulin in T2DM
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
DOSINGSEE REVERSE FOR TIPS
CHOOSE AN INSULIN CATEGORY
CHOOSE A BRAND
ADA-EASD Position Statement Update: Management of Hyperglycemia in T2DM, 2015
Long (Detemir)
Rapid (Lispro, Aspart, Glulisine)
Hours
Long (Glargine)
0 2 4 6 8 10 12 14 16 18 20 22 24
Short (Regular)
Hours after injection
Insu
lin le
vel
(Degludec)
3. ANTI-HYPERGLYCEMIC THERAPY
•Therapeutic options: Insulins
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 addedAdapted from Raccah D, et al. Diabetes Metab Res Rev 2007;23:257–64
Proper Basal titrationTitrate insulin
Clinical challenge:Selecting the appropriate treatment for your patient
Adapted from Nathan DM. N Engl J Med. 2007;356:437-40and Nathan et al. Diabetes Care. 2009;32:193-203
0.5-1.01.5 1.5 1.0-1.5 0.5-1.0 0.8-1.0
≥2.5
Sulfonylureas Biguanides(metformin) Glinides DPP-IV
inhibitors TZDs Insulin
0.0
0.5
1.0
1.5
2.0
2.5
3.0
HbA
1c r
educ
tion
(%
)
Efficacy as mono therapy
Anti diabetic agents
GLP-1agonists
Insulin is the most effectiveglucose-lowering agent
Management of
T2DM in Ramadan.
45
يام ( 183) يا أيها الذين آمنوا كتب عليكم الصكما كتب على الذين من قبلكم لعلكم تتقون
ريضا 184( عدودات فمن كان منكم م ) أياما م
ن أيام أخر وعلى الذين أو على سفر فعدة مع يطيقونه فدية طعام مسكين فمن تطوخيرا فهو خير له وأن تصوموا خير لكم إن
كنتم تعلمون
) شهر رمضان الذي أنزل فيه القرآن 185(ن الهدى والفرقان هدى للناس وبينات مهر فليصمه ومن كان فمن شهد منكم الش
ن أيام أخر يريد مريضا أو على سفر فعدة مالله بكم اليسر وال يريد بكم العسر ولتكملوا العدة ولتكبروا الله على ما هداكم ولعلكم
تشكرون
46
The Current decade…
Over the current decade, the number of fasting hours will progressively
increase in the northern hemisphere as Ramadan falls in the
summer months. This will have important implications
for Muslims with diabetes who wish to fast.
Raised Questions ……?
Ramadan Between Diabetes and Fasting
· Although the Koran exempts sick people from the duty of fasting, many Muslims with diabetes may not perceive themselves as sick and are keen to fast.
· 43% of patients with type 1 and 86% of those with type 2 diabetes fasted during Ramadan.
1-IBRAHIM SALTI, et al . Diabetes Care 27:2306–2311, 20042-E Hui et al , BMJ, 26 june 2010 , Volume 340
49
During Ramadan about 60% of patients change their antidiabetic drug intake:
35% stop treatment 8% change the dosage schedule 25% decrease the drug dose. Importantly, this is done at the
patients’ own initiative without medical supervision.
Salti I, Benard E, Detournay B et al. A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries. Diabetes Care 2004; 27: 2306–11.Aslam M, Healey MA. Compliance and drug therapy in Moslem patients. J Clin Hosp Pharm 1986; 11: 321–5.Aslam M, Assad A. Drug regimens and fasting during Ramadan: a survey in Kuwait. Public Health 1986; 100: 49–53.
The Risks of Fasting Include:
Hypoglycemia
Hyperglycemia
Diabetic ketoacidosis
Dehydration and thrombosis
M. al-Arouj et al, “Recommendations for management of diabetes during Ramadan,” Diabetes Care, 28(2005), 2305-2311.
12,243 subjects, in 13 countries including Egypt 1
Almost 90% was T2DM The important finding was: · 5 folds Increase in severe hyperglycemia with Ketoacidosis that required hospital
admission · 7.5 folds increase in the risk of severe hypoglycemia during Ramadan · 2% Of fasting patients experienced at least one episode of sever hypoglycemia
requiring hospitalization
1-IBRAHIM SALTI, et al . Diabetes Care 27:2306–2311, 20042- E Hui et al , BMJ 2010;340:c3053;
Classification of hypoglycemia according to severity: American Diabetes Association
1- Documented symptomatic hypoglycemia.
An event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration ≤ 70 mg/dl (3.9 mmol/l).
2- Asymptomatic hypoglycemia.
An event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration ≤ 70 mg/dl (3.9 mmol/l).
3- Probable symptomatic hypoglycemia.
An event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination.
4- Relative hypoglycemia.
An event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets those as indicative of hypoglycemia, but with a measured plasma glucose concentration >70 mg/dl (3.9 mmol/l).
5- Severe An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions.
52 American Diabetes Association Workgroup on Hypoglycemia. Defining and Reporting Hypoglycemia in Diabetes. Diabetes Care . 2005;28 (5):1245–1249.This material can only be shown reactively to answer specific questions from physicians.
Hypoglycemic Events Increased by 84% During Ramadan
Significant increasing in hypoglycemic events during Ramadan mainly with patients > 60 years old
Fatima J et al , Indian J Endocrinol Metab. 2012 Mar;16(2):323-4.
164
Num
ber o
f Hyp
ogly
cem
ic ev
ents
302
147
N= 179 84%
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
Neutrophilactivation
Plateletactivation
Factor VII
Blood coagulationabnormalities
Sympathoadrenal response
Inflammation
Endothelialdysfunction
Vasodilation
Heart rate variability
Rhythm abnormalities Haemodynamic changes Adrenaline Contractility Oxygen consumption Heart workload
HYPOGLYCAEMIA
54
Health and economical consequences of hypoglycemia
55This material can only be shown reactively to answer specific questions from physicians.
Hypoglycemia
CV complications2
Weight gain by defensive eating3
Coma2
Car accident4
Hospitalization costs1
Dizzy turn unconsciousness2
Seizures2
Death6
Increased risk of dementia5
Quality of Life7
1. Jönsson L, et al. Cost of Hypoglycemia in Patients with Type 2 Diabetes in Sweden. Value In Health. 2006;9:193–198 2. Barnett AH. CMRO. 2010;26:1333–13423. Foley J & Jordan. J. Vasc Health Risk Manag. 2010;6:541–5484. Canadian Diabetes Association’s Clinical Practice Guidelines for Diabetes and Private and Commercial Driving. CanJ Diabetes. 2003;27(2):128 –140.5. Whitmer RA, et al. JAMA. 2009;301:15655–15726. Zammitt NN, et al. Diabetes Care. 2005;28:2948–29617. McEwan P, et al. Diabetes Obes Metab. 2010;12:431–436
Hypoglycemia and Treatment Adherence
· Patients’ reports of hypoglycemic symptoms are associated with significantly lower treatment satisfaction and with barriers to adherence.
Alvarez Guisasola F, et al. Diabetes Obes Metab. 2008 Jun;10 Suppl 1:25-32.
Diabetic Ketoacidosis
Patients with type 1 diabetes and severe insulin deficiency may have excessive glycogenolysis, gluconeogenesis and ketogenesis. All of this may lead to hyperglycemia and ketoacidosis that may be life-threatening.
Karamat et al, J R Soc Med 2010: 103: 139–147.
DKA:Pathophysiology
beta-cell
alpha-cell
Loss of beta cell function is gradual over time
B L O O D
MUSCLE
DKA:Pathophysiology
Normal – glucose in blood
B L O O D
MUSCLEInsulin
Diabetic Ketoacidosis:Pathophysiology
Normal Mechanism
B L O O D
MUSCLE
1. Insulin deficiency*lack of glucose in muscle
2. glucagon excess*increase in gluconeogenesis
Diabetic Ketoacidosis:Pathophysiology
Insulin
Liver Glucagon
B L O O D
MUSCLEketones
Diabetic Ketoacidosis:Pathophysiology
3. Rapid lipolysis into free fatty acids and ketone bodies
release of Beta-hydroxybutyrate
ketones resoposible for all s&sketonesketones
ketones
B L O O D
MUSCLE
Diabetic Ketoacidosis:Pathophysiology
4. Hypovolaemia – vomitting + osmotic diuresis
Increases concentration of ketones + glucose
ketones
ketones
Dehydration and Thrombosis
Limitation of fluid intake
Hot and humid climates
Hard physical labor
Excessive perspiration.
Hyperglycemia• Osmotic
diuresis&
• Volume and electrolyte depletion.
Adapted from : M. al-Arouj et al, “Recommendations for management of diabetes during Ramadan,” Diabetes Care, 28(2005), 2305-2311.
Dehydration and Thrombosis
• Patients with diabetes exhibit a hypercoagulable state due to an increase in clotting factors, a decrease in endogenous anticoagulants, and impaired fibrinolysis.
• Increased blood viscosity secondary to dehydration may enhance the risk of thrombosis.
• A report from Saudi Arabia suggested an increased incidence of retinal vein occlusion in patients who fasted during Ramadan
M. al-Arouj et al, “Recommendations for management of diabetes during Ramadan,” Diabetes Care, 28(2005), 2305-2311.
Patients who insist on fasting need to be aware of the associated risks and be ready to adhere to the recommendations of their health care providers to achieve a safer fasting experience.
Al-Arouj M, et al. Diabetes Care. 2005;28(9):2305-11.
For Safer Fasting
Pre-Ramadan Medical Assessment
Management of Diabetic Patients During Ramadan
Safer Fasting
High
Moderate
Low risk of adverse events
Categories of risks for patients fasting Ramadan
E Hui et al , BMJ 2010;340:c3053; Al-Arouj M. et al, Recommendations for management of diabetes during Ramadan. Diabetes Care. 2010;33: 1895-1902.
High
Moderate
Low risk of adverse events
• Poor glycemic control, Severe and recurrent episodes of hypoglycemia.
• Experience ketoacidosis three months before Ramadan.
• Elderly and Pregnant women• Advanced complications
• Well controlled patients treated with short acting insulin secretogogue, sulphonylurea, insulin, or taking combination oral or oral plus insulin
• Well controlled patients treated with Metformin, Dipeptidyl peptidase-4 inhibitors, or thiazolidinediones who are otherwise healthy
E Hui et al , BMJ 2010;340:c3053; Al-Arouj M. et al, Recommendations for management of diabetes during Ramadan. Diabetes Care. 2010;33: 1895-1902.
Patients classed as high risk are advised not to fast Before Ramadan they must make necessary changes to their diabetes treatment
Those at low risk can fast without healthcare advice.
Cate
gorie
s of
risk
s fo
r
patie
nts
fast
ing
Ram
adan
Categories of risks for patients fasting Ramadan
Diabetic patients at risks during fasting:
Acute Peptic Ulcer Pulmonary Tuberculosis Bronchial Asthma Cancer Diabetes –Type 1 and 2
who have poor glycemic control (HbA1c >12%), non compliant with diet or drug/oral regimes, four OR more episodes of hypoglycemia AND/OR hyperglycemia during preceding month, on 2 and MORE insulin injection/day.
ESRD Cardiovascular disease Psychiatry Liver disorder, hepatic dysfunction where the liver enzyme is >> 2 x Upper
Normal Limit. Intercurrent infections
Pre-Ramadan Medical Assessment
Management of Diabetic Patients During Ramadan
Safer Fasting
Management of Diabetic Patients During Ramadan
Patients Education
T2DM Pharmaceutical Management in Ramadan
Four key areas in Ramadan focused education
1-
Meal
pl
anni
ng
and
di
et
ar
y
advic
e
2-Exercise
3-
Bl
ood
gl
ucose
monit
ori
ng
4-
Recogni
zi
ng
and
managi
ng
compli
cati
ons
E Hui et al , BMJ 2010;340:c3053;
Breaking the Fast
All patients must always and immediately end their fast if:
1. Hypoglycaemia (blood glucose of <60mg/dl).
2. Blood glucose reaches <70 mg in the first few hours after the start of the fast, especially if insulin, sulfonylurea drugs, or neglitinide are taken at predawn.
3. Blood glucose exceeds 300 mg with symptoms of hyperglycaemia.
Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010
Oral hypoglycaemic agents
Short acting insulin Sus
Take twice daily at suhur and iftar
TZDsNo treatment adjustment required 2–4 weeks to exert substantial antihyperglycemic effectsDPP4 inhibitors
The best tolerated drugs, Consider DPP4i if the risk of hypoglycemia is high.
SUs. Consider dose adjustment.
Metformin
Modify timing of doses:• Two thirds of dose at iftar• One third at suhur.
T2DM Pharmaceutical Management in Ramadan
E Hui et al , BMJ 2010;340:c3053; Al-Arouj M. et al, Recommendations for management of diabetes during Ramadan. Diabetes Care. 2010;33: 1895-1902.
77
Fasting during Ramadan in patients
on insulin therapy
78
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Time8:00
Physiological Serum Insulin Secretion Profile
79
Human Insulins and AnaloguesTypical Times of Action
Insulin Preparations
Onset of Action Peak Duration of Action
Aspart, glulisine, lispro
~15 minutes 1–2 hours 4–6 hours
Human regular 30–60 minutes 2–4 hours 6–8 hours
Human NPH, lente
2–4 hours 4–10 hours 12–20 hours
Premixed insulin
½ -1 hour 6-8hours 10-12 hours
GlargineDetemir
2–4 hours Flat ~24 hours12-20 hs (0.2-0.4 U/kg/d)
80
Action Profiles of Insulin Analogues
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Plasmainsulinlevels
Regular 6–8 hours
NPH 12–20 hours
Hours
Glargine or detemir 24 hours
Aspart, glulisine, lispro 4–6 hours
81
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00 8:00 12:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Time8:00
Basal/ Oral regimen
Bedtime NPH
50
Oral agents25
82
Time of day
20
40
60
80
100 B L D
Split-Mixed RegimenHuman Insulins
B=breakfast; L=lunch; D=dinner
0600 0600 0800 18001200 2400
NPHRegular
NPHRegular
Normal pattern
U/mL
83
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Time8:00
Twice daily premixed
84
Time of day
20
40
60
80
100 B L D
Multiple Daily Injections MDIHuman Insulins
B=breakfast; L=lunch; D=dinner
0600 06000800 18001200 2400
Regular NPHNPHRegular
Normal pattern
U/mLRegular
85
0600 0800 18001200 2400 0600
Time of day
20
40
60
80
100 B L D
Basal-Bolus Insulin TreatmentWith Insulin Analogues
B=breakfast; L=lunch; D=dinner
Glargine/ detemir
Lispro, glulisine, or aspart
Normal pattern
U/mL
86
Recommendations for Management of Diabetes During Ramadan for Patients on Insulin
The major objective of insulin therapy during Ramadan is to
provide adequate insulin to prevent the post meal hyperglycemia and also prevent hypoglycemia during the period of fasting
The choice of insulin therapy is decided by the previous therapy that the patient is taking and also the blood glucose profiles.
Ensure adequate fluid intake
87Aly A. Abdel-Rahim.
Bed time insulin
88
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00 8:00 12:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Time8:00
Basal/ Oral regimen
Bedtime NPH
50
Oral agents25
89
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Oral agents
Can NPH be used in Ramadan•Peak at a time which is not needed. NPH at breakfast•Will not cover breakfast.•Poor coverage of day time
90
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Oral agents
Can NPH be used in Ramadan
•Dangerous time of peakNPH after sohour
91
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00 8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Can peakless insulin replace NPH in Ramadan ??
•No peak, no hypoglycaemia.•Control meals with oral•Free time of injection
50
Oral agents25
basalinsulin
92
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Peakless insulin+ once daily oral secretagogue
basal insulin8-12 pm
Oral agent once
93
4:00
25
50
75
8:00 12:00 16:00 18:00 22:00 4:00
Plas
ma
Insu
lin µ
U/m
l)
Time8:00
One peakless Insulin + One Oral
OAD e.g DPP-4inhibitors Glargine Detemir
8-12PM
• No Peak• No Hypoglycemia• Control Iftar meal with OAD
94
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
50
25
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Peakless insulin+ premeal short acting oralsecretagogue
•Glinides offers ideal combination•Similar to intensive insulin therapywhen there is beta cell reserve•Adjust the dose according to the timeand size of meal
Short acting secretagogues basal insulin8-12 pm
95
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Short actingOral agents
Once daily premixed in Ramadan:once daily+ oral
•50/50 is better to control breakgast.•Short acting secretagogues additionalcontrol on sohour•Not suitable for exhausted beta cells
96Aly A. Abdel-Rahim.
Premixed insulin
97
4:00
25
50
75
8:00 12:00 16:00 18:00 22:00 4:00
Plas
ma
Insu
lin µ
U/m
l)
Time8:00
Twice Premix in Ramadan
98
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Twice daily premixed in Ramadan
•Fear of daytime hypoglycaemia•Overlap between sohour short acting andiftar intermediate acting
99
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Twice daily premixed in Ramadan
Dangerous even if dose size changed
100100
Ensure adequate fluid intake. 70/30 premixed insulin twice daily, e.g., 30 units
in morning and 20 units in evening……
In Ramadan,,,,,Use the usual morning dose at the sunset meal (Iftar) and half the usual evening dose at predawn (Suhur), e.g., 70/30 premixed insulin, 30 units at Iftar and 10 units at suhur.
Diabetes CareSeptember 2005 , pages 2305-11
Premixed insulin :
101
Premixed insulins Mix insulin 50/50 at iftar instead of Mix30
reduced postprandial glucose excursions and reduced hypoglycemia
Consider changing premixed insulin preparations to glargine or detemir plus lispro or aspart .
Mattoo V, Diabetes Res Clin Pract 2003;59:137-43
102
Time of day
20
40
60
80
100 B L D
Multiple Daily Injections MDIHuman Insulins
B=breakfast; L=lunch; D=dinner
0600 06000800 18001200 2400
Regular NPHNPHRegular
Normal pattern
U/mLRegular
103
Plas
ma
insu
lin (µ
U/m
l)
Aly A. Abdel-Rahim.
4:00
25
50
8:00 12:00 16:00 20:00 24:00 4:00Time
8:00
Peakless insulin+ premeal rapid acting insulin
basal insulin8-12 pm
Rapid acting insulin
104104
MOST patients will require short-acting insulin administered in combination with the intermediate, or long-acting insulin at the sunset meal to cover the large caloric load of Iftar & an
additional dose of short-acting insulin at predawn.
1. ADA. Diabetes Care 2006;29(suppl 1):S4–S42.
105
Patients on Basal insulin analogueglargine or detemir
It is advised that patients who take long
acting basal insulin, such as glargine, to reduce the dose by 20% to avoid hypoglycemia.
Continue taking the same doses of repaglinide or short acting insulin
106Aly A. Abdel-Rahim.
Advantages of rapid acting insulins
• Given at meal time not pre meal.• Can be modified according to the meal size.• Better post prandial profile.
107
PLEASE REMEMBER
108Aly A. Abdel-Rahim.
Remember
Patient education regarding fasting during theholy month of Ramadan is badly needed.
Diabetic patients with established renal diseaseare high-risk category.
Fasting for prolonged periods, especially in hotclimates, may impose negative impacts on renalfunction from hypovolemia and dehydration.
The mainstay of management of those patients istargeted toward arresting the progression of theirunderlying renal disease, and fasting duringRamadan should not be recommended.
109Aly A. Abdel-Rahim.
Remember
Patients with history of cerebrovascularaccidents or severe cardiovascular diseases aswell as those with critical limb ischamiashould be recommended not to fast.
Avoid long acting SU at sohour.
Metformin, TZDS, DPP4 inhibitors and glinidesare safe.
110
Remember
Careful use of intermediate- or long-acting insulin preparations plus a short-acting insulin administered before meals would be an effective strategy.
Adjustment to treatment necessary: e.g.· Reduce the dose of Basal insulin by 20%· Use Mix 50 in the evening instead of Mix 30
to avoid post prandial hyperglycemiaDiabetes Care 28.9 (Sept 2005): p2305(7).
111Aly A. Abdel-Rahim.
Treatment should be tailored and
adjusted
112
Some Parting Thoughts
“Fasting is for Me and I (Allah) only will reward it” (Hadith Qudsi)
“While fasting , if one does not give up falsehood in words and actions ,
then Allah has no need of him giving up food and drink (saying of Prophet
Muhammad-pbuh)”
HAVE A BLESSED RAMADAN
How to Help Patients Fast Safely ??
Patient Education Program.Individualization of anti diabetic drugsSelect more safe drugs.Adjust dose if neededEnsure good non – sugar fluid intake.Avoid heavy physical exercise at
afternoon.Ensure good calorie distribution.
Summary
Thank you