Should all diabetics with TB be on insulin?
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Transcript of Should all diabetics with TB be on insulin?
TB and Diabetes:
Should all diabetics with TB be on insulin?Iris Thiele Isip Tan MD, FPCP, FPSEM
Clinical Associate Professor, UP College of MedicineSection of Endocrinology, Diabetes & Metabolism, UP-PGH
http://www.endocrine-witch.info
Insulin
for Diabetics with TB
Drug effects/
interactions
1
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Rifampicin: a potent Cyt P450 inducerlowers the serum levels of SU and metformin
Guptan & Asha. Ind J Tub 2000
Rifampicin can induce CYP2C9-mediated metabolismModest reduction of plasma glimepiride concentration
“probably of limited clinical significance”
PlaceboRifamipicin
Niemi et al. Br J Clin Pharmacol 2000;50:591-595
Self & Morris. Chest 1980
Case report
62/M on chlorpropamide 250 mg daily
Given Rifampin 600 mg daily
Chlorpropamide increased to 400 mg daily
Case report
65/M on gliclazide 80 mg daily
FPG 6.4 mmol/L
HbA1c 5.4%
Atypical mycobacteriosis
Rifampicin, INH, EMB, Clarithromycin
FPG increased to 11.3 mmol/L
Gliclazide increased up to 160 mg daily
When rifampicin discontinued, gliclazide reduced to 80 mg daily (HbA1c 5.6%)
Sellers & Dean. Diabetes Care 2000
Drug-induced hepatitis with TB treatmentPrevalence: 9.7% (Malaysia) & 12% (HK)
Alcohol abuse and chronic hepatitis are independent risk factors
SU and Metformin
contraindicated in liver disease
Marzuki et al. Singapore Med J 2008;49(9):688Yew et al. Eu Resp J 1196;(9):389-90
Photo from Seattle Municipal ArchivesAccessed from http://www.flickr.com
Metformin can cause anorexia and GI discomfort1930’s case series: giving insulin for weight gain
“The use of insulin to cause a gain in weight in undernourished children and in lean but otherwise healthy adults is now a well-established procedure. It seems reasonable therefore to try its effects in undernourished persons
suffering from pulmonary tuberculosis.”
Heaton TG. Can Med Assoc J 1932;498-501
Conclusion“Insulin has a real place in the treatment of chronic
forms of pulmonary tuberculosis, febrile or afebrile, if the patient is undernourished. In some such cases
insulin is the best drug treatment we have.”
Heaton TG. Can Med Assoc J 1932;498-501
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Immunologic abnormalities in diabetes
Pulmonary physiologic dysfunction
Abnormal chemotaxis, adherence, phagocytosis and microbicidal function of PMNs
Diminished bronchial reactivity
Decreased peripheral monocytes with impaired phagocytosis
Reduced elastic recoil and lung volumes
Poor blast transformation of lymphocytes
Reduced diffusion capacity
Defective C3 opsonic functionOccult mucus plugging of airways
Reduced ventilatory response to hypoxemia
Worsened by hyperglycemia
Guptan & Shah. Ind J Tub 2000
TB infection produces glucose intolerance that improves or normalizes
with TB treatment
Not specific to TB, also seen in pneumonia
Jawad et al. J Pakistan Med Assoc 1995;45(9):237-8
Mycobacterial clearance from sputum is delayed during the first phase of treatment in patients with diabetesDiabetes: independent risk factor for a 5-delay in
mycobacterial clearance within first 60 days
Restrepo et al. Am J Trop Med Hyg 2008;79(4):541-4
n=496
Diabetes increased risk of active pulmonary TB only in
those with HbA1c >7%
Leung et al. Am J Epid 20008;167:1486-94
Active Adj HR 3.11 [95%CI 1.63-5.92, p =0.001)
Culture confirmed Adj HR 3.08 [95%CI 1.44-6.57, p =0.004)
Pulmonary Adj HR 3.11 [95%CI 1.79-7.33, p <0.001)
Diabetics had 6.5x higher odds [95%CI 1.1-3.80,
p=0.039] of dying from TB than non-diabetics
Relationship between severity of diabetes and TB outcomes
could not be evaluated
Dooley et al. Am J Trop Med Hyg 20009;80(4):634-9
Unclear if tight diabetes control would have a positive impact on treatment
outcomes of those with active TB
Qing Zhang et al. Jpn J Infect Dis 20009;62:390-391
Qing Zhang et al. Jpn J Infect Dis 2009;62:390-391
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Management of Coexistent TB and DM
Patients with poor diabetic control should be hospitalized for stabilizing their blood sugar level.
Ideally, insulin should be used to control blood sugar levels.
Oral hypoglycemics should be used only in cases of mild diabetes. Drug interaction with rifampicin should be kept in mind.
Goals of therapy: FPG 120 mg/dL and HbA1c <7%
Guptan & Shah. Ind J Tub 2000
Indications for insulin in type 2 diabetes with TB
Chronic and severe tuberculosis infection
Loss of tissue and function of pancreas
Requirement of high calorie, high protein diet
Interactions and adverse effects of anti-TB drugs
Associated hepatic disease
Contraindications for oral antidiabetic drugs
Aging
Rao PV. Int J Diab Dev Countries 1999
Brazilian Thoracic
Association2009
TB in Diabetics“Consider extending treatment to 9 months and replace oral hypoglycemic agents with insulin during treatment
(keep fasting glycemia <160 mg/dL).”
BTA Committee on Tuberculosis & BTA Tuberculosis Working Group J Bras Pneumol 2009;35(10):1018-1048
Who should be started on insulin?
On Metformin with A1c >8.5%
Not reaching A1c target of OHA combination therapy
Kidney/liver dysfunction where OHA is contraindicated
Severe uncontrolled diabetes with catabolism
ADA-EASD 2008 Algorithm. Diabetes Care 31:1-11, 2008
Who should be immediately started on insulin?
Severely uncontrolled diabetes with catabolism
Fasting BG >13.9 mmol/L (250 mg/dL)
Random BG consistently > 16.7 mmol/L (300 mg/dL)
A1c > 10%
Presence of ketonuria
Symptomatic diabetes: polyuria, polydipsia, weight loss
ADA-EASD 2008 Algorithm. Diabetes Care 31:1-11, 2008
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Glycemic Targets for Type 2 Diabetes
Healthy ADA 1 AACE 3 IDF 4ADA-
EASD 5
Hba1c (%)* <6.0 1 <7.0 + <6.5 <6.5 <7.0 +
FBG, mmol/L (mg/dL)
<5.6 2
(<100)5.0-7.2 (90-130)
<6.0 (<110)
<6.0 (<110)
3.9-7.2 (70-130)
PPBG, mmol/L (mg/dL)
<7.8**2
(<140)<10.0**
<7.8 (<140)
<8.0**(<145)
<10(<180)
1. 1 American Diabetes Association. Diabetes Care 2006;29(suppl 1):S4–S42.2. 2 American Diabetes Association. Diabetes Care 2006;29(suppl 1):S43–8.3. 3 American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):40–82.4. 4 International Diabetes Federation. Global Guideline for Type 2 Diabetes. Brussels: International
Diabetes Federation, 2005. http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf.5. 5 Nathan D. et al. Diabetologia 2006;49:1711–21.
*DCCT-referenced assays: normal range 4–6%; **1–2 hours postprandial. †ADA and ADA/EASD guidelines recommend HbA1C levels ‘as close to normal (<6%) as possible without significant hypoglycemia’1,5
ADA=American Diabetes Association; AACE=American Association of Clinical Endocrinologists;IDF=International Diabetes Federation; EASD=European Association for the Study of Diabetes.
Expected Decrease in A1c
Step 1: initial
•Lifestyle change: 1-2%
•Metformin: 1.5%
Step 2: additional therapy
•Basal insulin: 1.5-2.5% (at least)
•Sulfonylureas: 1.5%
•TZDs: 0.5-1.4%
•GLP-1 agonist: 0.5-1.0%
Basal insulin
6.0
6.5
7.0
7.5
8.0
8.5
9.0
SU TZD
HbA1c
ADA-EASD Consensus. Nathan et al Diabetes Care 2006
Indications for insulin
3
Immune dysfunction
2
Treatment goals
4Insulin
for Diabetics with TB
Drug effects/
interactions
1
Thank You!http://www.endocrine-witch.info