A MANAGEMENT OF TYPE 2 DIABETES MELLITUS AND HYPERGLYCEMIC

HYPEROSMOLAR STATE IN A PATIENT WITH PULMONARY TUBERCULOSIS

Ismayadi

INTRODUCTION
Type 2 diabetes mellitus(DM) tipe 2 a group of metabolic diseases characterized by
hyperglycemia resulting ranging from predominantly insulin resistance with relative insulin
deficiency to predominantly an insulin secretory defect with insulin resistance (American
Diabetes Association, 2016). Poorly controlled diabetes can lead to susceptibility or severity
oftuberculosis, conversely tuberculosis can worsen glycemic control (Dooley & Chaisson,
2009; Perkeni, 2015). In the rarely case, tuberculosis can precipitate crisis of hyperglycemia
include hyperglycemic hyperosmolar state and diabetic ketoacidosis (Rao, 1999; Van
Cromphaut et al., 2008; Kibirige, 2014).
Many studies reported that tuberculosis and diabetes mellitus are two diseases that affect
each other. Globally, the prevalence of tuberculosis related diabetes mellitus was estimated
15%, whereas most of diabetes mellitus and tuberculosis cases was undiagnosed or late
diagnosis (Riza et al., 2014).
Patient with DM and tuberculosis can have more severe clinical manifestations,
higherrisks of treatment failure and death on treatment, and increased rates of recurrent
tuberculosis after treatmenthas been completed.There are many uncertainties aboutoptimum
treatment strategies for patients with dualdisease, including the length of tuberculosis
treatment,appropriate dosages of the antibiotic rifampicin and oral sulphonylurea derivatives
due to potential drug to druginteractions, and increased drug toxicity (Kapur et al., 2016).
DM and tuberculosis are two disease that affect each other to worsening of the clinical
manifestation, cause complications, and potentially interfere the therapy, therefore we will
discuss about a management diabetes mellitus (DM) accompanied by tuberculosis and
hyperglycemic hyperosmolar state (HHS).

Case
A man, 50 years old, came to emergency room with seizure 4 times since 3 hours before
admitted, without weakness in part of the body, thick in the face, headache, loss of speech,
nausea, and vomiting.
Since 4 months admitted, patient complaint productive cough, sputum yellowish,
shortness of breath, mild fever, night sweat, weakness, and low appetite.
Case Report Department of Internal Medicine Airlangga University School Medicine Dr. Soetomo
Teaching Hospital Surabaya November 3, 2016

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 Since about 2 weaks admitted, patient complaint weakness, shortness of breath, more
often lie in bed and unable to work, eating about 4-5 spoons, and alone at home because his
wife and children work.
The patient had denied loss of weight, excessive eating, thirst, or urinate, bloody cough,
chest pain, abdominal pain, toothache, earache, sore throat, and diarrhea. No pain on forehead,
on either side of nose, in upper jaws and teeth, or between eyes.
History of past illness: pulmonary tuberculosis (3 months before admitted). Denied
diabetes mellitus, hypertension, stroke.
On physical examination, found general weakness, GCSE4-V3-M6 and 3 hours laters
GCS E4-V5-M6. Blood pressure 130/90 mmHg, pulse 92 x/minute regular, respiratory rate 20
x/minute, and temperature 36.90C, no deficit of neurologic.
On examination of head and neck, found dry mouth, no pallor of conjunctiva, no icteric
of sclera, no cyanosis, no dyspnea, no found tooth decay, and no found signs of infection in
nose, ear, throat, dan sinuses. No enlargement of lymph nodes and no increased of jugular vein
pressure (JVP). On chest examination, found normal and symmetry chest, normal respiratory
movement. On pulmonary examination, found normal fremitus, vesicular breath sound, ronchi
sound on upper-right of hemithorax and no wheezing. On cardiac examination, found ictus
cordis at left midclavicular line of ICS V, heart sound S1 & S2 single without murmur, gallop,
or extrasistole. On examination of abdomen, found flat, supple, no tenderness, and normal
intestinal sound. Liver and spleen were not enlargement. On examination of extremities, no
found edema, the acral was red, warm, and dry. On examination of skin, found decrease of
turgor and no found petechiae, pustule, bullae, squama, or rash. Body weight 54 kg, height
166 cm, and IMT 19.60.
Laboratory result at emergency room was found hemoglobin (Hb) 12.2 gr/dl, WBC 13,700/uL,
granulocyte 77%, platelet 455,000/uL, lymphocyte 2,200/uL,and monocyte 1.000/uL. Random
blood glucose (RBG) 705 mg/dl, albumin 4.03 gr/dl, BUN 10.4 mg/dl, serum creatine
1.37 mg/dl, AST 10 U/L, ALT 16 U/L, CRP 7.44 mg/L, serum sodium 143 mmol/L, serum
potassium 2.6 mmol/L, serum chloride 101 mmol/L,rapid test of HbsAg negative, and rapid
test of HIV non-reaktive. Arterial Blood Gas analysis (BGA) before rehydration pH 7.225,
pCO2 41.0 mmHg, pO2 247.5 mmHg, HCO3 17.1 mmol/L, Base Excess -10.7 mmol/L, and
SO2 99.7%. serum osmolarity 325.17 mOsm/kg. BGA after rehydration pH 7.49, pCO2
34.0 mmHg, pO2 95 mmHg, HCO3 25.9 mmol/L, Base Excess 2.6 mmol/L, and SO2 98%.
Urinalysis result after rehydration color yellow, pH 7.0,SG 1.015, glucose3+, bilirubin
negative, keton negative,protein 2+, nitrit negative, leukosit negative, erithrocyte 5-10/lp, and
leukocyte 2-5/lp.On chest x-ray (AP position, asymmetric) found fibro-infiltrate at right and
left suprahilar with upper-right schwarte. On head CT-Scan without contrast no found
abnormality.

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 According on history, physical examination, laboratory and imaging result, the working
diagnosis of this patient is type 2 diabetes mellitus, pulmonary tuberculosis, hyperglycemic
hyperosmolar state (HHS), serial general clonic seizure ec. metabolic encephalopathy,
moderate dehydration, and hypokalemia. The planning of diagnostic is serial random blood
glucose (RBG), fasting blood glucose (FBG), 2-hours blood glucose (2-h BG), HbA1C, serial
serum electrolyte, lipid profile, and acid fast bacilli (AFB) sputum. The planning of therapy is
on phase 1 with rehydration NaCl 0,9% 2 litre in 2 hours, then be continued NaCl 0,9% 80
gtt/minute in 4 hours, and then be continued 30 gtt/minute in 18 hours, then be continued NaCl
0,9% 20 gtt/minute in 24 hours; rapid acting insulin (RCI) 4 unit intravena 6x, and KCl
50 mEq inRL 500 ml in 12 hours. Therapy on phase 2 with diet B1 2,100 kcal/day, fluid
balance, insulin rapid-acting 3 x 14 iusubcutan before eating, maintenance balance of serum
electrolyte, and anti-tuberculosis drugs. The planning of monitoring is signs and symptoms,
vital signs, and urine production.
The progress of disease
2nd day, complaint cough with yellowish sputum, little eating or drinking. Urine output
1,300 ml/24 hours,RBG 204 mg/dl,and serum potassium 2,9mmol/L. Working diagnosis:
type 2 diabetes mellitus, pulmonary tuberculosis, hyperglycemia hyperosmolar state (HHS),
moderate dehydration, hypokalemia, and serial general clonic seizure ec. metabolic
encephalopathy. The therapy continued with addition phenytoin 100 mg iv was dissolved in
20 ml NaCl 0,9% per drip every 8 hours in 1-2 minute, novorapid 3 x 14 unit inj. sc. ac.,
alinamin F 2 x 1 amp.inj. iv., and Diazepam 1 amp. inj. iv.if seizure.
3th day, urine production 1,600 ml/24 hours, WBC 13,300/uL, granulocyte 73.6%, RBG
180 mg/dl, and serum potassium 2. hyperosmolar state (HHS), moderate dehydration, and
hypokalemia. The therapy continued.
5th day, urine production 1,600 ml/24 jam and acid fast bacilli (AFB) of sputum +++.
Working diagnosis : type 2 diabetes mellitus and pulmonary TB. The therapy continued with
addition the intensive phase of the first-line of anti-tuberculosis drugs (Rifampicin 450 mg,
isoniazid (INH) 300 mg, Pyrazinamide 1.000 mg, Ethambutol 1.000 mg). Monitoring
symptoms, signs, vitals signs, and urine production.
7th day, urine production 2,000 ml/24 hours. The result of laboratory HbA1C 8.6, WBC
11,500/ul, granulocyte 70.2%,FBG 135 mg/dl,2-h BG 220 mg/dl,and serum potassium
3.8 mmol/L. Working diagnosis: type 2 diabetes mellitus and pulmonary TB. The therapy
continued with addition Levemir 1x10 unit sc (night). The patient was discharged.
Discussion
Diabetes mellitus (DM) is Diabetes is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The etiologic
classification of diabetes mellitus is 4 type : (1) type 1 diabetes, (2) type 2 DM, (3) other
specific diabetes and, (4) gestational diabetes. The etiologic of type 2 diabetes may range from

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predominantly insulin resistance with relative insulin deficiency to a predominantly secretory
defect with insulin resistance (Perkeni, 2015; ADA, 2016).
Diabetes caused 1.5 million deaths in 2012. Higher-than-optimal blood glucose caused
an additional 2.2 million deaths, by increasing the risks of cardiovascular and other diseases.
Globally, an estimated 422 million adults were living with diabetes in 2014, compared to
108 million in 1980 (WHO, 2016).
The clinical manifestation of diabetes mellitus include polyuria, polydipsia, weight
loss, sometimes with polyphagia, blurred vision, fatigue, tingling/pain/numbness in the
hand/feet, dysfunction of penile erection, and prurity of vulvae (Perkeni, 2015).
Diagnosis criteria of diabetes include : (1) fasting blood glucose (FBG) ≥126 mg/dl or;
(2) 2-hours blood glucose (2-h BG) ≥200 mg/dl during the oral glucose tolerance test (OGTT)
or; (3) random blood glucose (RBG) ≥200 mg/dl with classic symptoms of hyperglycemia or
hyperglycemic crisis or; (4) HbA1c ≥6.5% (Perkeni, 2015; ADA, 2016).
This patient was a man, 50 years old, with feeling very thirsty, fatigue, seizure, without
history of diabetes, lethargy, tachycardia, and RBG 705 mg/dl with hyperglycemic
hyperosmolar state. HbA1C 8.6, FBG 135 mg/dl, and 2-h BG 220 mg/dl.
Hyperglycemia or poorly glycemic control in diabetes can increase susceptibility to
infection lead to HHS (Perkeni, 2015). Pulmonary tuberculosis is a infection disease at
pulmonary parenchym caused by Mycobacterium tuberculosis (Kemenkes RI, 2013). In 2012,
globally, There is estimated about 15% of tuberculosis case that associated with diabetes and
about 10% in Indonesia. The risk of TB is increased by 2-3 fold in individu with diabetes
compared by general population (Dooley &Chaisson, 2009; Ruslami, 2010).
Some difficulties in management of TB with DM include worse anti-tuberculosis
treatment outcomes with longer times to sputum culture conversion, increased risk of death or
treatment failure, and increased risk of recurrent TB after successful completion of treatment.
Conversely, TB, like other infections, can worsen glycaemic control and complicate the
clinical management of DM. Poorly controlled diabetes can lead to multiple complications,
including vascular disease, neuropathy, and increased susceptibility to infection. Diabetes
might also lead to increased susceptibility to disease caused by M tuberculosis via multiple
mechanisms. The mechanism sinclude those directly related to hyperglycaemia and cellular
insulinopenia, as well as indirect effects on macrophage and lymphocyte function, leading to
diminished ability to contain the organism. It is not clear why DM patients, particularly those
with poorly controlled disease, are at increased risk ofTB, although changes have been found
in both the irinnate and their adaptive immune responses. Theexact mechanisms underlying
this susceptibility to TB are still relatively undefined and are in need of detailed evaluation.
(Dooley &Chaisson, 2009; Harries, 2015).
The clinical manifestation of pulmonary tuberculosis include coughing up blood or
sputum that lasts 2 weeks or longer, dyspnea, fatigue, low appetite, weight loss, malaise,

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sweating at night, or fever 1 month or longer. Further more, there is found by breath sound
bronchial, amphoric, decreased of breath sound, ronchi, and retraction signs of pulmonary,
diaphragm, and mediastinum. On chest x-ray was found by opacity or nodular shadow at apex
segment and posterior of superior lobe lobe and inferior lobe of upper segment, cavity, military
nodule, and pleural effusion. The diagnosis of pulmonary tuberculosis is established according
by bacterilogic examination include direct microscopic examination, culture, and rapid test
(Kemenkes RI, 2013).
On 3 months before admitted, this patient has diagnosed by pulmonary tuberculosis but
refused to take a medicine. Since 4 months before admitted, this patient was often coughing
with yellowish sputum, shortness of breath, and fever, sweating at night, fatigue, and loss of
appetite. On chest x-ray, there had found fibroinfiltrate shadow at right and left suprahilar
with a schwarte at upper suprahilar. Result of fast acid bacilli test of sputum was +++. This
patient was diagnosed by new case of pulmonary tuberculosis..
Infection is the most common of precipitation factor that trigger HHS. The others of
precipitation factor of HHS are pancreatitis, myocardial infarction, cerebrovascular accident,
trauma, high glucose drink, drugs include corticosteroid, corticosteroids, sympathomimetic
agents, thiazides, and second generation antipsychotic agents. The energy demand is increased
by infection that lead to increase secretion of counterregulatory hormones (Goodman, 2003;
Corwellet al., 2014). Although rare, the tuberculosis can precipitate HHS (Rao, 1999; Van
Cromphaut et al., 2008; Kibirige, 2014). HHS has been estimated to account for approximately
1% of diabetic admissions and the mortality in HHS is ranging from 10% to 20% (Maletkovic
& Drexler, 2013).
Hyperglycemia is caused by increase of hepatic glucose production and decrease of
glucose utility in liver, muscle, and adipose tissue, as a result of synergistic actions insulin
deficiency (relative of absolute) and increase the level of counterregulatory hormones
(Goodman, 2003; Gerard, 2014). Hyperglycemia causes fluid depletion which be resulted by
two primarily factors include osmotic diuresis and insulin deficiency. A state in low intake of
fluid, The osmotic diuresis can lead to hipovolemia and decrease of GFR that might worsen
hyperglycemia and loss of serum electrolyte include sodium and potassium. Deficiency of
insulin causes loss of water and electrolyte as result of decrease effect of insulin to water and
electrolyte resorption on renal tubule. Depletion of body fluid and hyperglycemia lead to
hyperosmolarity of plasma cause intracellular fluid shift to extracellular. Decreased of plasma
hyperosmalarity lead to neurologic dysfunction that characterized by irritability, restlessness,
stupor, muscular twitching, hyperreflexia, spasticity, seizure, coma, and death (Verbalis, 2007;
Kitabchi et al., 2009; Pasquel&Umpierrez, 2014).
Mostly, patient with HHS is elderly and have unknown diabetes. HHS may develop
insidiously over daysto weeks. Signs and symptoms of HHS include classic symptoms of

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hyperglycemia, impaired vision, seizure, mental change, and signs of dehydration (Kitabchi et
al., 2009).
The diagnosis criteria of HHS include: (1) plasma glucose level > 600 mg/dl; (2)
arterial pH >7.30; (3) serum bicarbonate >15 mEq/L; (4) no/minimal ketosis; (5) serum
osmolarity >320 mOsm/Kg; (6) anion gap <12; (7) change of mental state or occasionally
neurologyc disorders (Kitabchiet al., 2009). In Dr. Soetomo Hospital, we use diagnostic
criteria, that called by HHS pentalogy, include: (1) plasma glucose level ≥ 600 mg/dl; (2) no
history of DM; (3) no Kusmaul respiratory; (4) no ketonuria; (5) plasma osmolarity ≥ 325
mOsmol/Kg; with supported by arterial pH >7,30, serum bicarbonate >18 mEq/L, anion gap
<12, mental/neurologyc disorders; pre-renal azotemia, severe dehydration (Tjokroprawiro &
Murtiwi, 2016).
This patient is a man, 50 years old, found feeling a thirsty, fatigue, seizure, no history
of diabetes, low intake of water, dry mouth, tachycardia, decreased of skin turgor, low urinate
(<100 ml before rehydration), lethargy, and random blood glucose 705 mg/dl.
Arterial BGA before rehydration is pH 7.225, pCO2 41.0 mmHg, pO2 247.5 mmHg,
HCO3 17.1 mmol/L, Base Excess -10.7 mmol/L, and SO2 99.7%. Serum osmolarityis 325.17
mOsm/kgand anion gap 3.1 mEq/L, no ketonuria, and serum potassium 2.6 mmol/L.
Management protocol of HHS include fluid, decrease the blood glucose level by insulin
and potassium replacement as seen at figure 1 (Kitabchi et al., 2009). At Dr. Soetomo hospital,
there is two phase of HHS management : phase 1 (initial) and phase 2 (if blood glucose level ±
250 mg/dl or reduction +). On phase 1 include : (1) fluid replacement with formula “2-4-18-
24”; (2) insulin rapid acting; (3) potassium replacement; (4) antibiotic. The fluid replacement
with isotonic fluid (ringer lactate or NaCl 0,9%) 2 litre in 2 hours, then continued by 80
gtt/minute in 4 hours, then continued by 30 gtt/minute in 18 hours, and then continued by 20
gtt/minute in 24 hours. Insulin therapy with use formula “minus 1” by intravenous bolus
injection or “X 12’ by intravenous continue infusion. Hold insulin therapy when initial serum
potassium level is less < 3,3mEq/L. On phase 2 include : maintenance therapy of fluid,
maintenance of serum electrolyte balance, insulin therapy, and adequate nutrition. When the
patient could eat and ketosis was resolved, then give insulin with use formula “X2”
subcutaneous injection. Potassium replacement use formula “Hypo K-1234” until serum
potassium level >3,5mEq/L : serum potassium 3.0 – 3.5 mEq/L give 25 mEqKCl in 24 hours;
serum potassium 2.5 – 3.0 mEq/L give 50 mEqKCl in 24 hours; serum potassium 2.0 – 2.5
mEq/L give 75 mEqKCl in 24 hours; serum potassium <25 mEq/L give 25 mEqKCl in 5 hours.
KCl dissolved in isotonic fluid (NaCl 0,9% atau Ringer laktat) (Tjokroprawiro, 2014).
This patient was received fluid replacement with NaCl 0,9%, on phase 1, given 2 litre
in 2 hours, then continued by 80 gtt/minute in 4 hours, then continued by 30 gtt/minute in 18
hours, and then continued by 20 gtt/minute in 24 hours. fluid maintenance was given 20
gtt/minute isotonic fluid. Given RCI with use formula “minus 1” : insulin 4 unit every hour 6

6
times and check blood glucose every 3 hours. When blood glucose 204 mg/dl, then given
insulin novorapid 14 unit subcutaneous injection before breakfast, lunch, and dinner. The
insulin therapy was given without unknown of serum potassium level. When the result of serum
potassium 2.6 mmol/L, then given potassium replacement with use “Hypo K-2” : KCl 50 mEq
dissolved in 500 ml RL for 12 hours. This patient refused installation CVC.

Figure 1.Management Protokolof DKA and HHS on adult patient (Kitabchiet al., 2009).

The treatment of tuberculosis consist of 2 phase : intensive phase and continuation

phase. First line regiment of intensive phase include Isoniazid (INH), Rifampicin, Pyrazinamid,
Ethambutol, danStreptomysin. The treatment of pulmonary tuberculosis consist of : (1) new
case; (2) patient with history of first-line therapy and; (3) patient with multi-drug resistant
(MDR). Guideline of anti-tuberculosis regiment for new case that recommended is
2RHZE/4HR (Kemenkes RI, 2013). When blood glucose is controlled, no difference guideline
of tuberculose treatment on TB without DM and TB with DM. When blood glucose in
uncontrolled, the treatment is continued until 9 months (Dooley & Chaisson, 2009).
This patient had diagnosed by new case of pulmonary tuberculosis. Given first-line
regiment 2RHZE/4HR : on intensive phase Rifampicin 450 mg, INH 300 mg, Pyrazinamid
1000 mg, dan Ethambutol 750 mg. On continuation phase, INH 300 mg and Rifampicin
450 mg.
The treatment of DM include oral anti-diabetic drugs and insulin. There are five groups
of oral anti-diabetic drugs : (1) insulin secretagogue : sulphonylurea and glinid; (2) insulin
sensitizer : metformin and thiazolidinediones; (3) glucose absorption inhibitor : alpha
glucosidase inhibitor; (4) DPP-IV inhibitor; (5) SGLT-2 inhibitor. The drugs of sulphonylurea

7
group are glibenclamide, glipizide, gliclazide, gliquidone, and glimepiride. Drugs of glinid are
repaglinide and nateglinide. Thiazolidinediones drug is pioglitazone. The drug of alpha
glucosidase inhibitor is acarbose. The drugs of DPP-IV inhibitor are vildagliptin, sitagliptin,
saxagliptin, andlinagliptin. The drug og SGLT-2 inhibitor is dapaglifozin. There are 7 types of
insulin include (1) rapid-acting : lispro, aspart, andglulisin; (2) short-acting; (3) intermediate-
acting; (4) long-acting : glargineanddetemir; (5) ultra long-acting : degludec; (6) human
premixed; (7) analog premixed (Perkeni, 2015).
Optimal glycemic control might improve outcome of tuberculosis therapy and prevent
complication of DM. Therefore, it is recommended a aggressive approach of diabetes
management on patients with TB. There are 4 factors that influence glycemic control of patien
with DM during treating tuberculosis include (1) active tuberculosis, the inflammation lead to
insulin resistant, low appetite, and loss of weight that influence glucose homeostasis;
conversely, TB treatment causes effects : decrease inflammation and increase appetite, weight,
and activity; (2) behavior : intake of varied foods, exercise, and therapy compliance; (3) drugs
therapy : adverse, interaction, and weight target during therapy; (4) health system.
Effect therapy of some drugs of oral anti-diabetic (OAD) is decrease when given with
rifampicin. Rifampicin is a inducer potent that induce metabolism enzimes, i.e. cytochrome
P450 (CYP). Induction of these enzymes can lead toaccelerated metabolism of drugs given
with rifampicin and reduced treatment effect. Induction of cytochrome P450 (CYP) is fully
reached in one weeks after given rifampicin and the induction might loss in 2 weeks after
rifampicin stopped. Some drugs of oral anti-diabetic was induced by cytochrome P450 (CYP).
Therefore, effect therapy of oral anti-diabetic (OAD) might decreased when given with
rifampicin. Oral anti-diabetic drugs that its metabolism is mediated by cytochrome P450
(CYP) are sulphonylurea (glyburide, gliclazide, glimepiride, and glipizide) and nateglinide
with CYP2C9 enzyme, repaglinide and thiazolidinediones with CYP2C8, and glinide group
(repaglinide and nateglinide), linagliptin, saxagliptin, and sitagliptin with CYP3A4.
Sulphonylurea have strongly hypoglycemic effect, then monitoring of blood glucose should be
performed, primarily after rifampicin therapy stopped (Tornio et al., 2012). Rifampicin might
decreased serum concentration of OAD drugs by 22 – 65% include glyburide, glipizide,
rosiglitazone, pioglitazone, nateglinide, and repaglinide. Insulin requirements mightincrease
when on rifampicin. Rifampicin has been shown to cause early-phasehyperglycaemia with
associated hyperinsulinaemia even in non-diabetic patients. Rifampicin's direct and indirect
effects on glycaemic control make careful monitoring with appropriate dose adjustment of
diabetic agents essential in diabetic patients with tuberculosis (Dooley & Chaisson, 2009).
Therapy effect of metformin, alpha glucosidase inhibiotor, and vildagliptin might not
influenced by rifampicin since this drugs is not mediated by cytochrome P450. Possible
disadvantages of metformin use in patients with tuberculosis include the risk of gastrointestinal
side effects and, very rarely, lactic acidosis (Tornio et al., 2012). Overlapping toxicities must

8
also be considered when co-managing tuberculosis and diabetes, such as peripheral neuropathy
caused by treatment with isoniazid. Given the risk ofperipheral neuropathy, pyridoxine should
be given with isoniazid during tuberculosis treatmentin diabetic patients (Dooley & Chaisson,
2009).
Just as tuberculosis drug treatment affects diabetes treatment, diabetes might alter the
pharmacokinetics of antituberculosis drugs. In one study in Indonesia, diabetic patients with
tuberculosis had rifampicin serum concentrations that were 53% lower than in non-diabetic
patients with tuberculosis, and there was an indirect relation between fasting glucose and
rifampicin concentrations. 103 Given that low concentrations of anti-tuberculosis drugs have
been linked to treatment failure or resistance, this finding is of particular concern. Diabetes can
also cause changes in oral absorption, decreased protein binding of drugs, and renal
insufficiency or fatty liver with impaired drug clearance.104 Its effect on tuberculosis drug
concentrations has not been formally studied; in cases of poor response to treatment in diabetic
patients with tuberculosis, therapeutic drug monitoring might be considered. (Dooley &
Chaisson, 2009).
Insulin use at the start of tuberculosis treatment has been suggested; some national
treatment guidelines (for instance in Indonesia) strongly suggest the use of insulin for diabetes
in patients with tuberculosis even though no evidence base lends support to that approach.
Because insulin is not metabolised, it has no pharmacokinetic interactions with rifampicin or
other antituberculous drugs, but insulin has several potential drawbacks when used in under-
resourced settings including cost, availability, storage, and delivery. (Rizaet al., 2014).
Therapy on discharged for this patient is insulin novorapid 15 iusubcutan before
breakfast, lunch, and dinner; levemir 10 iusubcutan at night.
The prognosis of patient with DM and TB is good if controlled blood glucose.
However, tuberculosis often relapse although had gotten complete treatment (Kemenkes RI,
2013).
This patient was in therapy of tuberculosis and diabetes. During treatment on ward,
HHS and hypokalemia had resolved, while blood glucose was uncontrolled.

Summary
It was reported a man, 50 years old, with complaint seizure and chronis coughing with
yellowish sputum. The patient had meet the type 2 diabetes mellitus, pulmonary tuberculosis,
and hyperosmolar hyperglycemic state (HHS). HHS might be triggered by pulmonary
tuberculosis. This patient had received diet B1, fluid replacement, insulin, hypokalemia, and
anti-tuberculosis drugs. Furthermore, this patient would routinely controlled at inpatient
department of Dr. Soetomo hospital. This patient had good prognosis.

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