This document discusses Diabetic Ketoacidosis (DKA), a life-threatening complication of diabetes that occurs when there is a severe lack of insulin. It presents when blood sugar levels rise, fat is broken down instead of glucose, and acid builds up in the blood. Symptoms include nausea, vomiting, and fruity breath. DKA is most common in type 1 diabetes but can occur in other types during illness or medication changes. Treatment involves fluids, electrolytes, and insulin to stabilize the condition. Cerebral edema is a risk, especially in children, where the swelling can be fatal if not addressed.

1. mwebazavictor1997@gmail.com
MBChB 6th YEAR
UGANDAN
Kampala international university western
campus Jinja site light
JINJA REGIONAL REFERRIAL HOSPITAL JRRH
Internal Medicine Department
DIABETIS MELLITUS AND ITS
COMPLICATIONS PRESENTATION
Moderator : DR. KIBUUKA AFIZI
(consultant JRRH)
07th /March/2023 7am
MWEBAZA VICTOR

2. ETHICAL DISCUSSION
"Scope and impact of financial conflicts of interest in biomedical research: a systematic review". JAMA. 289 (4): 454–65.
doi:10.1001/jama.289.4.454. PMID 12533125.

3. History about diabetes mellitus
1. Diabetes was one of the first diseases described, with an
Egyptian manuscript from 1500 BC mentioning "too great
emptying of the urine." The Ebers papyrus includes a
recommendation for a drink to take in such cases. The first
described cases are believed to have been type 1 diabetes.
2. Indian physicians around the same time identified the
disease and classified it as madhumeha or "honey urine",
noting the urine would attract ants.
3. The term "diabetes" was first used in 230 BC by the Greek
Apollonius of Memphis.
4. The disease was considered rare during the time of the
Roman empire, with Galen commenting he had only seen
two cases during his career. Galen named the disease
"diarrhea of the urine" (diarrhea urinosa).

4. madhumeha Apollonius of Memphis

5. Two types of diabetes were identified as separate
conditions for the first time by the Indian physicians
Sushruta and Charaka in 400–500 CE with one type
being associated with youth and another type with
being overweight.
The term "mellitus" or "from honey" was added by the
Briton John Rolle in the late 1700s

6. PA RT 1
Diabetes
Diabetes mellitus (DM), commonly known as diabetes, is a group
of metabolic disorders characterized by a high blood sugar level
over a prolonged period of time.
Diabetes is a chronic heterogeneous metabolic disorder
Characterized by Hyperglycemia due to defects in:
Insulin secretion, Insulin action, or both.
World Health Organization. Archived from the original on 31 March 2019. Retrieved 4 April 2019.

7. WORLD diabetic mellitus epidemiological
picture

15. AFRICAN Diabetes mellitus epidemiological
pictures

18. UGANDA diabetes mellitus
epidemiology

22. As of 2019, an estimated 463 million people had
diabetes worldwide (8.8% of the adult population),
with type 2 diabetes making up about 90% of the
cases.
Rates are similar in women and men.
In 2019, diabetes resulted in approximately
4.2 million deaths. It is the 7th leading cause of
death globally. The global economic cost of diabetes
related health expenditure in 2017 was estimated
at US$727 billion.
"Deaths and Cost | Data & Statistics | Diabetes | CDC". cdc.gov. 20 February 2019. Archived from the original on 19 June
2019. Retrieved 2 July 2019.

24. Type 1 diabetes Due to
pancreas's failure to produce
enough insulin due to loss of
beta cells aka "insulin-
dependent diabetes mellitus"
(IDDM) or "juvenile
diabetes".
Gestational diabetes is the
third main form, and occurs
when pregnant women
without a previous history
of diabetes develop high
blood sugar levels.
Diabetes is due to either the pancreas not producing enough insulin, or
the cells of the body not responding properly to the insulin produced.
There are three main types of diabetes mellitus:
WHO. October 2020. Archived from the original on 26 August 2018. Retrieved 25 March 2022.
RSSDI textbook of diabetes mellitus (Revised 2nd ed.). Jaypee Brothers Medical Publishers. 2012. p. 235. ISBN 978-93-5025-
489-9. Archived from the original on 14 October 2015.
Type 2 diabetes begins with
insulin resistance, a condition
in which cells fail to respond to
insulin properly. As the disease
progresses, a lack of insulin
may also develop. aka "non
insulin-dependent diabetes
mellitus" (NIDDM) or "adult-
onset diabetes". The most
common cause is a
combination of excessive body

25. Other types
Maturity onset diabetes of the young (MODY) is
a rare autosomal dominant inherited form of
diabetes, due to one of several single-gene
mutations causing defects in insulin
production.
See table next page please.
"Monogenic Forms of Diabetes". National institute of diabetes and digestive and kidney diseases. US NIH. Archived from the
original on 12 March 2017. Retrieved 12 March 2017.

29. Feature Type 1 diabetes Type 2 diabetes
Onset Sudden
Gradual
Age at onset Mostly in children
Mostly in adults
Body size Thin or normal Often obese
Ketoacidosis Common Rare
Autoantibodies Usually present
Absent
Endogenous insulin
Low or absent Normal, decreased
or increased
Concordance
in identical twins
50% 90%
Prevalence ~10% ~90%
Williams textbook of endocrinology (12th ed.). Elsevier/Saunders. 2011. pp. 1371–1435. ISBN 978-1-4377-
0324-5.

32. Signs and symptoms
The classic symptoms of untreated diabetes are
unintended weight loss, polyuria , polydipsia ,
and polyphagia . Symptoms may develop rapidly
(weeks or months) in type 1 diabetes, while they
usually develop much more slowly and may be
subtle or absent in type 2 diabetes.
In addition to the known ones above, blurred
vision, headache, fatigue, slow healing of cuts,
and itchy skin. Prolonged high blood glucose
diabetic retinopathy,diabetic dermadromes
WHO | Diabetes mellitus". WHO. Archived from the original on 2004-06-11. Retrieved 2019-03-23.
Rockefeller, J.D. (2015). Diabetes: Symptoms, Causes, Treatment and Prevention. ISBN 978-1-5146-0305-5. Archived from
the original on 2020-08-01. Retrieved 2020-08-05.

34. INSULIN
The most potent anabolic hormone known Promotes the
synthesis of Carbohydrates, lipids and proteins while
inhibiting their degradation and release into the circulation
The most powerful physiologic stimulus is increased
circulating blood glucose. Insulin secretion is inhibited by
hypoglycemia, epinephrine and norepinephrine .Insulin in
the circulation is decreased in long term starvation.

35. PHASES OF INSULIN RELEASE
The first phase of insulin secretion begins within 2 min of
nutrient ingestion and continues for 10–15 min
The second phase of prandial insulin secretion is
sustained until normoglycemia is restored.

36. Levels of blood sugar
(glucose) regulate secretion
of hormones from
the pancreas
Pancreas secretes insulin
when glucose levels are high
Insulin binds to insulin
receptors on fat and muscle
and “promotes” glucose
uptake
Overall effect: blood glucose
levels return to normal
GLUCOSE HOMEOSTASIS

38. Glucose transport
Cell membranes are not inherently permeable to glucose.
Glucose-transporter (GLUT) proteins carry glucose through
the membrane into cells.
1. GLUT-1 - enables basal non-insulin-stimulated glucose
uptake into many cells
2. GLUT-2 - transports glucose into the β cell: a prerequisite for
glucose sensing.
3. GLUT-3 - enables non-insulin-mediated glucose uptake into
brain neurons and placenta.
4. GLUT-4 - enables much of the peripheral action of insulin. It
is the channel through which glucose is taken up into muscle
and adipose tissue cells following stimulation of the insulin
receptor

40. Diagnosis; WHO diabetes diagnostic criteria
Condition 2-hour glucose
Fasting glucose
HbA1c
mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT %
Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0
Impaired
fasting
glycaemia
< 7.8 < 140 6.1–7.0 110–126 42–46 6.0–6.4
Impaired
glucose
tolerance
≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4
Diabetes
mellitus
≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5
Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: Report of a WHO/IDF consultation (PDF). Geneva: World Health
Organization. 2021. p. 21. ISBN 978-92-4-159493-6.

41. PART 2
COMPLICATIONS OF
DM
Ethical Cultural concerns
1. Cultural differences can create difficult medical
ethics problems. Some cultures have spiritual or
magical theories about the origins and cause of
disease, for example, and reconciling these beliefs
with the tenets of Western medicine can be very
difficult.
2. As different cultures continue to intermingle and
more cultures live alongside each other, the
healthcare system, which tends to deal with
important life events such as birth, death and
suffering, increasingly experiences difficult
dilemmas that can sometimes lead to cultural
clashes and conflict. Efforts to respond in a culturally
sensitive manner go hand in hand with a need to
distinguish limits to cultural tolerance.
ETHICAL EDUCATION CORNER

42. Diabetic emergencies
People (usually with type 1 diabetes) may also
experience episodes of diabetic ketoacidosis (DKA),
hyperosmolar hyperglycemic state (HHS), which is
more common in type 2 diabetes and is mainly the
result of dehydration.
Hyperglycaemia, Diabetic comma, Hypoglycemia
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (July 2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32 (7): 1335–
43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476. Archived from the original on 2016-06-25.

44. Complications of diabetes
Acute complication
1. Diabetic ketoacidosis (DKA)
2. Hyperglycemia
hyperosmolar state
3. Hypoglycemia
4. Diabetic coma
Chronic complication
Microangiopathy
1. Diabetic nephropathy
2. Diabetic neuropathy
3. Diabetic retinopathy
4. Diabetic encephalopathy

45. Macrovascular disease
Macrovascular disease leads to cardiovascular
disease, to which accelerated atherosclerosis is a
contributor:
1. Coronary artery disease,
2. Diabetic myonecrosis
3. Peripheral vascular disease,
4. Stroke (mainly the ischemic type)
5. Carotid artery stenosis does not occur more
often in diabetes, and there appears to be a
lower prevalence of abdominal aortic aneurysm.

47. 1 . Diabetic ketoacidosis DKA
Diabetic ketoacidosis (DKA) is a potentially life-
threatening complication of diabetes mellitus.
DKA happens most often in those with type 1
diabetes but can also occur in those with other
types of diabetes under certain circumstances.
Misra, S; Oliver, NS (28 October 2015). "Diabetic ketoacidosis in adults" (PDF). BMJ (Clinical Research Ed.). 351: h5660. doi:10.1136/bmj.h5660.
hdl:10044/1/41091. PMID 26510442. Archived (PDF) from the original on 9 December 2019. Retrieved 1 November 2017.

48. SYMPTOMS AND SIGNS OF DKA
1. Hx/o Nausea and vomiting,
pronounced thirst, excessive
urine production and abdominal
pain , Kussmaul breathing.
2. On physical examination there
is usually clinical evidence of
dehydration, a ketotic odor,
increased respiratory rate.
3. Small children with DKA cerebral
oedema, which may cause
headache, coma, loss of the
pupillary light reflex, and can
progress to death. It occurs in
about 1 out of 100 children with
DKA and more rarely occurs in
adults.
CAUSES OF DKA
1. DKA most frequently occurs in
DM1
2. May also occur in intercurrent
illness (pneumonia, influenza,
gastroenteritis, a urinary tract
infection),
3. pregnancy,
4. inadequate insulin administration
(e.g. defective insulin pen device),
5. myocardial infarction (heart
attack), stroke or the use of
cocaine.
6. Drugs like gliflozin class (SGLT2
inhibitors), which are generally
used for type 2 diabetes, have
been associated with cases of DKA
Goldenberg, RM; Berard, LD; Cheng, AYY; Gilbert, JD; Verma, S; Woo, VC; Yale, JF
(December 2016). "SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and
Recommendations for Prevention and Diagnosis". Clinical Therapeutics. 38 (12): 2654–
2664.e1. doi:10.1016/j.clinthera.2016.11.002. PMID 28003053.

49. mechanism/patho physiological changes in DKA
1. The lack of insulin and corresponding elevation of glucagon
leads to increased release of glucose by the liver from glycogen
via glycogenolysis and also through gluconeogenesis. High
glucose levels spill over into the urine, taking water and solutes
(such as sodium and potassium) along with it in a process
known as osmotic diuresis. This leads to polyuria, dehydration,
and polydipsia.
2. The absence of insulin also leads to the release of free fatty
acids from adipose tissue (lipolysis), which are converted
through a process called beta oxidation, again in the liver, into
ketone bodies (acetoacetate and β-hydroxybutyrate). β-
Hydroxybutyrate can serve as an energy source in the absence
of insulin-mediated glucose delivery, and is a protective
mechanism in case of starvation. The ketone bodies, however
lead to metabolic acidosis.
3. Bicarbonate buffering system is quickly overwhelmed and
other mechanisms must work to compensate for the acidosis
and this lead to Kussmaul respiration.

50. The clinical state of DKA is associated, in addition to
the above, with the release of various
counterregulatory hormones such as glucagon and
adrenaline as well as cytokines, the latter of which
leads to increased markers of inflammation, even in
the absence of infection.
For Cerebral edema ,The swelling of brain tissue leads
to raised intracranial pressure ultimately leading to
death.
Dunger DB, Sperling MA, Acerini CL, et al. (February 2004). "European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine
Society consensus statement on diabetic ketoacidosis in children and adolescents". Pediatrics. 113 (2): e133–40. doi:10.1542/peds.113.2.e133.
PMID 14754983. Archived from the original on 2009-09-12
Brown TB (March 2004). "Cerebral oedema in childhood diabetic ketoacidosis: Is treatment a factor?". Emergency Medicine Journal. 21 (2): 141–
4. doi:10.1136/emj.2002.001578. PMC 1726262. PMID 14988335. Archived from the original on 2016-04-13
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (July 2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32 (7): 1335–
43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476. Archived from the original on 2016-06-25.
Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 2152–2180. ISBN 978-0-07-139140-5.

51. The American
Diabetes
Association
categorizes DKA in
adults
Description by ADA for DKA.
Mild: 1. blood pH mildly decreased to between 7.25 and 7.30
(normal 7.35–7.45);
2. serum bicarbonate decreased to 15–18 mmol/l (normal
above 20);
3. the person is alert
Moderate: 1. pH 7.00–7.25,
2. bicarbonate 10–15,
3. mild drowsiness may be present
Severe: 1. pH below 7.00,
2. bicarbonate below 10,
3. stupor or coma may occur
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (July 2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes
Care. 32 (7): 1335–43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476. Archived from the original on 2016-06-25.

52. Differential diagnosis of DKA
1. Alcoholic ketoacidosis
2. Acute appendicitis
3. Hyperosmolar
hyperglycemic
nonketotic coma
4. Hypokalemia
5. Hyponatremia
6. Lactic acidosis
1. Metabolic acidosis
2. Myocardial infarction
3. Pneumonia
4. Septic shock
5. Salicylate toxicity
6. Urinary tract infection
7. Uremia

53. Resting point
To diagnose diabetic ketoacidosis, one must find: D= Diabetes (hyperglycemia) K=
Ketosis (ketonemia/ketonuria) A= Acidosis
A23 year old Female is brought to the hospital after being found unconscious by her
family in the house with noted difficult in breathing as reported by the boy friend .
However She was dxed with diabetes mellitus at the age of 16 and since then on
insulin therapy with poor drug adh due to hard access to insulin
1. What are your immediate concerns about this patient?
2. How will you grade the condition.
3. What are possible of coma in any patient @ medical ward ?
4. What is at the top of your differential diagnosis?
5. What risk factors does the patient have for developing DKA?
6. What physical findings are you looking for?
7. How will you manage and investigate apatient with DM1.

54. Management of DKA
Fluid replacement therapy FRT
If dehydration is so severe as to cause shock ,rapid
infusion of saline (1 liter for adults, 10 ml/kg in
repeated doses for children) is recommended to
restore circulating volume. Slower rehydration
based on calculated water and sodium shortage
may be possible if the dehydration is moderate,
and again saline is the recommended fluid.
"Type 1 diabetes in adults: diagnosis and management". National Institute for Health and Care Excellence. August 2015.
Archived from the original on 9 August 2016. Retrieved 10 February 2016.

55. According to UCG
Normal saline (NaCl 0.9%)
15-20 ml/kg in the first hour (500-1000 ml)
Children: 10-20 ml/kg
Continue with 5-15 ml/kg/hour according to vital
signs, urinary output, and clinical condition
If blood sugar <14 mmol/L, switch to dextrose 5%
if ketones still present, and/or clinical condition not
yet normal (patient unable to eat)

56. Insulin Therapy
Some guidelines recommend a bolus (initial large
dose) of insulin of 0.1 unit of insulin per kilogram of
body weight. This can be administered immediately
after the potassium level is known to be higher than
3.3 mmol/l

57. In general, insulin is given at 0.1 unit/kg per hour to
reduce the blood sugars and suppress ketone
production. Guidelines differ as to which dose to
use when blood sugar levels start falling; some
recommend reducing the dose of insulin once
glucose falls below 16.6 mmol/l (300 mg/dl) but
other recommend infusing glucose in addition to
saline to allow for ongoing infusion of higher doses
of insulin.

58. According to uganda medical / clinical
guidelines recommend
Soluble insulin 4-6 IU IM every hour until
condition stabilises
Child >5 years: 0.1 IU/kg/hour
Child <5 years: 0.05 IU/Kg/hour
Continue insulin until ketosis resolves, and
patient is able to eat

59. TYPE OF
INSULIN
USUAL
PROTOCOL
ACTION
ONSET PEAK DURATION
Insulin
short acting,
regular
soluble (e.g.
Actrapid)
3 times
daily, 30
minutes
before
meals
30
Min
2–5
hrs
5–8
hrs
Insulin
intermediate
acting,
NPH, (e.g.
Insulatard)
Once or
twice daily
(evening ±
morning)
1–3
hrs
6–12
hrs
16–24
hrs
Insulin
biphasic,
mixture of
regular and
NPH (e.g.
Mixtard
30/70)
Once or
twice daily
30
min
2–12
hrs
16–24
hrs

60. Preferably, a combination of intermediate and
short acting insulin should be used, in the
following regimens e.g.,
Pre-meals short acting insulin (e.g. actrapid), and
1. evening intermediate acting insulin (e.g.
Insulatard). The evening dose should be 40-
50% of the daily dose (basal-bolus therapy) OR
2. Twice daily premixed insulin Mixtard: usually
2/3 of total dose in the morning and 1/3 in the
evening, 30 minutes before meals

61. NOTICE and CAUTION ON INSULIN Rx
Note
Patients on insulin should measure their blood
glucose level at least twice daily (before
breakfast, and before dinner), and insulin doses
adjusted accordingly
Caution
Oral antidiabetic medicines are NOT used in type 1.
Metformin can be used but only under specialist
advice

62. Potassium electrolyte collection K+ Therapy
Potassium levels can fluctuate severely during the
treatment of DKA, because insulin decreases
potassium levels in the blood by redistributing it into
cells via increased sodium-potassium pump activity.
A large part of the shifted extracellular potassium
would have been lost in urine because of osmotic
diuresis.
Addition of potassium to the intravenous fluids once
levels fall below 5.3 mmol/l.
If potassium levels fall below 3.3 mmol/l, insulin
administration may need to be interrupted to allow
correction of the hypokalemia.

63. According to UCG
If potassium level not available
Add potassium chloride 1 ampoule in every 1 litre of
infusion as soon as the patient has started passing
urine
If potassium levels available:
1. K <3.5 mmol/L: add 40 mmol (2 ampoules) per 1
litre of fluid
2. K 3.5-5.5 mmol/L: add 20 mmol (1 ampoule) per 1
litre of infusion
3. K >5.5 mmol/L: do not add any potassium

64. Additional therapy in DKA
o Sodium bicarbonate therapy.
The administration of sodium
bicarbonate solution to rapidly
improve the acid levels in the
blood is controversial.
Its use is discouraged, although
some guidelines recommend it
for extreme acidosis (pH<6.9),
and smaller amounts for severe
acidosis (pH 6.9–7.0).
o Cerebral edema
Cerebral edema, if associated with
coma, often necessitates
admission to intensive care,
artificial ventilation, and close
observation. The administration
of fluids is slowed. The ideal
treatment of cerebral edema in
DKA is not established, but
intravenous mannitol and
hypertonic saline (3%) are used—
as in some other forms of
cerebral edema—in an attempt
to reduce the swelling
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (July 2009).
"Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32
(7): 1335–43. doi:10.2337/dc09-9032. PMC 2699725. PMID 19564476.
Archived from the original on 2016-06-25.

65. Resolution of DKA
Defined as general improvement in the symptoms,
such as the ability to tolerate oral nutrition and
fluids, normalization of blood acidity (pH>7.3),
and absence of ketones in blood (<1 mmol/l) or
urine.
Once this has been achieved, insulin may be
switched to the usual subcutaneously
administered regimen, one hour after which the
intravenous administration can be discontinued
Joint British Diabetes Societies Inpatient Care Group (March 2010). "The Management of Diabetic Ketoacidosis in Adults". NHS Diabetes.
Archived from the original (PDF) on 2012-05-04. Retrieved 2012-05-01.

66. 2 . HYPEROSMOLAR HYPERGLYCEMIC
STATE HHS
Hyperosmolar hyperglycemic state (HHS) is a
complication of diabetes mellitus in which
high blood sugar results in high osmolarity
without significant ketoacidosis.
The main risk factor is a history of diabetes
mellitus type 2.
"Hyperosmolar hyperglycemic state". American Family Physician. 71 (9): 1723–30. PMID 15887451.
Pasquel, FJ; Umpierrez, GE (November 2014). "Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and
treatment". Diabetes Care. 37 (11): 3124–31. doi:10.2337/dc14-0984. PMC 4207202. PMID 25342831.

67. Signs and symptoms of HHS
Hx/o of high blood sugar
including increased
thirst , increased
volume of urination and
increased hunger
Signs of HHS include:
o Altered level of
consciousness
o Neurologic signs
including: blurred
vision, headaches, focal
seizures, myoclonic
jerking, reversible
paralysis
oMotor abnormalities including
flaccidity, depressed reflexes,
tremors or fasciculations
oHyperviscosity and increased risk
of blood clot formation
oDehydration
oWeight loss
oNausea, vomiting, and abdominal
pain
oWeakness
oLow blood pressure with standing

68. Triggers, risk factors to HHS
Triggers include infections, stroke, trauma, certain
medications, and heart attacks.
Risk factors:
1. Lack of sufficient insulin (but enough to prevent ketosis)
2. Poor kidney function
3. Poor fluid intake (dehydration)
4. Older age (50–70 years)
5. Certain medical conditions (cerebral vascular injury,
myocardial infarction, sepsis)
6. Certain medications (glucocorticoids, beta-blockers,
thiazide diuretics, calcium channel blockers, and
phenytoin)

69. Pathophysiology of HHS
Glucose is usually higher than 33 mmol/L
(600 mg/dL), and a resulting serum osmolarity that
is greater than 320 mOsm.
This leads to excessive urination (more specifically an
osmotic diuresis), which, in turn, leads to volume
depletion and hemoconcentration that causes a
further increase in blood glucose level.
Ketosis is absent because the presence of some
insulin inhibits hormone-sensitive lipase-mediated
fat tissue breakdown.

70. Diagnosis of HHS by ADA
According to the American Diabetes Association ;
1. Plasma glucose level >30 mmol/L (>600 mg/dL)
2. Serum osmolality >320 mOsm/kg
3. Profound dehydration, up to an average of 9L (and
therefore substantial thirst (polydipsia))
4. Serum pH >7.30
5. Bicarbonate >15 mEq/L
6. Small ketonuria (~+ on dipstick) and absent-to-low
ketonemia (<3 mmol/L)
7. Some alteration in consciousness
8. BUN > 30 mg/dL (increased)
9. Creatinine > 1.5 mg/dL (increased)
Henry, McMichael (2016). ATI RN Adult Medical Surgical Nursing 10.0. Assessments Technology Institutes. pp. 537–538. ISBN 9781565335653.

71. Management of HHS
Intravenous fluids
Treatment of HHS begins with reestablishing
tissue perfusion using intravenous fluids.
People with HHS can be dehydrated by 8 to
12 liters. Attempts to correct this usually take
place over 24 hours with initial rates of normal
saline often in the range of 1 L/h for the first
few hours or until the condition stabilizes.
Tintinalli, Judith E.; Kelen, Gabor D.; Stapczynski, J. Stephan; American College of Emergency Physicians (2004). Emergency Medicine: A Comprehensive Study
Guide (6th ed.). McGraw-Hill Prof Med/Tech. p. 1309. ISBN 978-0-07-138875-7. Archived from the original on 24 March 2017.

72. Electrolyte replacement
Potassium replacement is often required as the
metabolic problems are corrected. It is
generally replaced at a rate 10 mEq per hour
as long as there is adequate urinary output.
Tintinalli, Kelen & Stapczynski 2004, p. 1320

73. Insulin
Insulin is given to reduce blood glucose
concentration; however, as it also causes the
movement of potassium into cells, serum
potassium levels must be sufficiently high or
dangerously low blood potassium levels may
result. Once potassium levels have been verified
to be greater than 3.3 mEq/l, then an insulin
infusion of 0.1 units/kg/hr is started. The goal for
resolution is a blood glucose of less than
200 mg/dL.
Henry, McMichael (2016). ATI RN Adult Medical Surgical Nursing 10.0. Assessments Technology Institutes. pp. 537–538. ISBN 9781565335653.

74. Management of Type 2 Diabetes
First line Mgt;
Life style modifications
–– If sugar levels not very high, and patient is willing, try
lifestyle modifications for 3 months, and reassess
If lifestyle modifications not enough, and/or sugar level
initially very high, start on:
Metformin 1.5-2 g daily in divided doses at meals (start with
500 mg once a day for one week,then increase by 500 mg
every week until target control is achieved)

75. 1. If treatment targets not achieved with
lifestyle modifications and metformin, add a
second line drug.
2. If intolerance or contraindication to
metformin, start directly with second line

76. Second line Mgt;
Glibenclamide 5 mg once daily with meals, initially
Elderly: 2.5 mg daily adjusted according to response up to
a maximum of 10 mg in divided doses
Glimepiride 1-4 mg once daily before or with the first
meal of the day
Start with lowest dose, and increase every 1-2 weeks
according to response
o If control not achieved, add basal insulin (third
line)

77. Third line Mgt;
Insulin SC NPH (Insulatard) 8 IU (or 0.3 IU/Kg) in
the evening, increase by 2-4 IU every 3-7 days
until fasting blood glucose is in range
If control still not achieved, consider a full
insulin regimen. Stop
glibenclamide/glimepiride, but maintain
metformin if possible

78. Caution on Glibenclamide,met4min,
and oral anti diabetics
1. Glibenclamide: Use with caution/lower doses
in elderly patients because of risk of
prolonged hypoglycaemia. Preferably use
glimepiride if available.
2. Metformin is contraindicated in advanced
kidney disease
3. Do not use oral anti-diabetics in acute
complications, and in acutely sick patients: use
insulin for initial management

79. Final Relaxing point.
A 87 y/o male dxed with DM since he was 79yrs with a
poor drug adh due to financial issues , presented with
h/o increased thirst , increased volume of urination and
increased hunger, altered mental states, on admin @
emergency unit of Jinja hospital the RBS was
43.3mmol/l .
1. What can be the complication in the pt.
2. What are the other complication associated with DM.
3. How will you investigate and also manage the pt.

80. 3 . DIABETIC
RETINOPATHY
Diabetic retinopathy, is a
medical condition in which
damage occurs to the retina
due to diabetes mellitus.
"Diabetic retinopathy". Diabetes.co.uk. Retrieved 25 November 2012.
It is a leading cause of blindness in developed countries in age
range of 30 to 65 years.
The condition typically develops about 10–15 years after
receiving the diagnosis of diabetes mellitus.

81. Diabetic retinopathy is the result of damage to the
small blood vessels and neurons of the retina.
The earliest changes leading to diabetic retinopathy
include narrowing of the retinal arteries associated
with reduced retinal blood flow; dysfunction of the
neurons of the inner retina, followed in later stages
by changes in the function of the outer retina,
associated with subtle changes in visual function.

82. Later, the basement membrane of the retinal blood
vessels thickens, capillaries degenerate and lose
cells, particularly pericytes and vascular smooth
muscle cells.
This leads to loss of blood flow and progressive
ischemia, and microscopic aneurysms which appear
as balloon-like structures jutting out from the
capillary walls, which recruit inflammatory cells;
and advanced dysfunction and degeneration of the
neurons and glial cells of the retina.
Xu H, Curtis T, Stitt A (13 August 2013). "Pathophysiology and Pathogenesis of Diabetic Retinopathy [internet]". Diapedia.
7104343513 (14). doi:10.14496/dia.7104343513.14. Retrieved 26 August 2016.

83. Clinical picture
1. DRpy often has no early
warning signs, Patients may
not notice the signs and have
20/20 vision.
2. symptoms; blurry vision,
vision loss, blindness
3. The only way to detect DRpy
is by fundus examination
4. On funduscopic exam, a
doctor will see cotton wool
spots, flame hemorrhages,
and dot-blot hemorrhages
5. On addition to complete eye
examination for example
visual acuity test, etc
On funduscopic exam
1. Leaking blood vessels
/retinal haemorrhage,
presents with haemorrhagic
dots and blot.
2. Retinal swelling, such as
macular edema,
3. Pale, fatty deposits on the
retina (exudates) – signs of
leaking blood vessels,
4. damaged nerve tissue
(neuropathy) leading
cotton wool spots.
5. any changes in the blood
vessels.

85. Complications and risk factors
1. Vitreous hemorrhage
2. Retinal detachment
3. Glaucoma
4. Blindness
The risk factor is diabetes
Treatment of DRpy
Medications
1. Intravitreal triamcinolone acetonide Triamcinolone is a long acting
steroid preparation.
2. Intravitreal anti-VEGF There are good results from multiple doses of
intravitreal injections of anti-VEGF drugs such as bevacizumab.
3. Topical medications There is little evidence for the role of topical
medications in the treatment of macular edema, for example, topical
non‐steroidal anti‐inflammatory agents
There are three major treatments
for diabetic retinopathy, which are
very effective in reducing vision
loss from this disease
1. Laser photocoagulation
2. Medication
3. Surgical management
forexample vitrectomy

86. 4 . DIABETIC NEPHROPATHY
Diabetic kidney disease (DKD), also known as
diabetic nephropathy, is the long-term
decreased in kidney function due to diabetes

87. Signs and symptoms
The onset of symptoms is 5 to 10 years
after the disease begins.
1. nocturia
2. tiredness
3. headaches
4. general feeling of illness
5. nausea, vomiting
6. frequent daytime urination,
7. lack of appetite
8. itchy skin
9. leg swelling
The clinical presentation of diabetic
nephropathy (DN) is characterized
by proteinuria , hypertension and
progressive loss of kidney function .
Risk factors
1. Poor control of blood glucose
2. Uncontrolled high blood
pressure
3. Type 1 diabetes mellitus, with
onset before age 20
4. Past or current cigarette use
5. A family history of diabetic
nephropathy- certain genes
eg APOL1, which has been
found to be associated with
nephropathy in African
American individuals.
6. Certain racial groups (African
Americans, Mexican
Americans, and Pima Indians
are at higher risk).

88. Pathophysiology
The disease progression of DN involves various clinical
stages:
1. Hyperfiltration
2. Microalbuminuria
3. Macroalbuminuria
4. nephrotic proteinuria to progressive chronic kidney
disease leading to end-stage renal disease (ESRD).
The damage is exerted on all compartments of the
kidney

89. Diagnosis of diabetic nephropathy
Diagnosis is based on the measurement of abnormal levels of
urinary albumin in a diabetic coupled with exclusion of other
causes of albuminuria. Albumin measurements are defined as
follows:
1. Normal albuminuria: urinary albumin excretion <30 mg/24h;
2. Microalbuminuria: urinary albumin excretion in the range of
30–299 mg/24h;
3. Macroalbuminuria: urinary albumin excretion ≥300 mg/24h
Urinary albumin excretion can also be measured by urinary
albumin/creatinine ratio in a spot urine sample, which is as
accurate but more convenient than a 24-hour urine
collection.

90. Staging of Diabetic nephropathy
CKD Stage
CKD Stage eGFR level (mL/min/1.73 m2)
Stage 1 ≥ 90
Stage 2 60–89
Stage 3 30–59
Stage 4 15–29
Stage 5 < 15
Biomarkers
Although albuminuria is the most frequently used marker of DN, it has a limited
sensitivity as many patients with DN experience GFR loss and glomerulosclerosis
without immediate elevation in albuminuria.
Many novel markers are currently being studied that potentially detect DN at earlier
stages and identify progression risk. Cystatin C is a protein that is freely filtered in the
glomeruli before it is reabsorbed and catabolized in the renal tubular cells. Its serum
level is independent of muscle mass, making more accurate at estimating GFR than
creatinine serum levels.

91. Management of diabetic nephropathy
Management of diabetic nephropathy currently
centers over four main areas:
1. Cardiovascular risk reduction
2. glycemic control
3. blood pressure control
4. inhibition of the RAAS system.

92. Emerging therapies
A relatively new medication that has been approved for
treatment for DM is sodium glucose cotransporter 2
(SGLT2) inhibitors.
The mechanism of action of this drug is to the sodium-
glucose uptake cotransporter in the proximal tubule,
thereby generating naturesis and glucosuria.
In multiple clinical trials, SGLT2 inhibitors showed improved
cardiovascular outcomes in patients with DM as well a
positive effect on kidney outcomes, mainly a reduction in
albuminuria and progression of renal damage. Other
classes of diabetic medications that have been shown to
have a positive effect on the progression of DN are GLP-1
agonists and DPP-4 inhibitors
Heerspink, Hiddo J.L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I. (2016-09-06). "Sodium Glucose Cotransporter 2 Inhibitors in
the Treatment of Diabetes Mellitus". Circulation. 134 (10): 752–772. doi:10.1161/circulationaha.116.021887. ISSN 0009-7322. PMID 27470878.

93. 5 . DIABETIC NEUROPATHY
Diabetic neuropathy is nerve damage due to
diabetes
This is a relatively early and common
complication affecting approximately 30% of
diabetic patients .
National Institute of Diabetes and Digestive and Kidney Diseases. Archived from the original on
19 May 2021. Retrieved 3 August 2021.

94. Signs and symptoms
Diabetic neuropathy can affect
any peripheral nerves
including sensory neurons,
motor neurons, and the
autonomic nervous system.
Therefore, diabetic neuropathy
has the potential to affect
essentially any organ system
and can cause a range of
symptoms. There are
several distinct syndromes
based on the organ systems
affected.
1. Peripheral: Numbness,
tingling, or weakness of
the limbs
2. Autonomic: Urinary
incontinence, gastro
paresis, sexual dysfunction
3. Focal: Carpel tunnel,
cranial neuropathy
4. Cranial neuropathy
Risk factors 1. Poorly controlled
diabetes
2. being overweight
3. high blood
pressure
4. high cholesterol
5. kidney disease
6. Alcohol
7. smoking

95. complication
1. Diabetic foot
2. Intestinal obstruction
3. CN Palsies disorders
4. Stroke
Treatment
1. Blood sugar control
2. Medications , Medication
options for pain control
include antiepileptic drugs
(AEDs), serotonin-
norepinephrine reuptake
inhibitors (SNRIs), and tricyclic
antidepressants (TCAs)
Anticonvulsant are better for short
pain relief.
Multiple guidelines recommend
antiepileptics, such as
pregabalin, as first-line
treatment for painful diabetic
neuropathy
Prevention
Diabetic neuropathy can be largely
prevented by maintaining blood
glucose levels and lifestyle
modifications.

96. 3 . Physical therapy
4 . Others for example botulinum toxin injection
5 . Medical devices for example Transcutaneous
electrical nerve stimulation (TENS) and interferential
current (IFC)
NOTICE
There is insufficient evidence to draw firm conclusions
for the utility of the cannabinoids nabilone and
nabiximol.
Waldfogel JM, Nesbit SA, Dy SM, Sharma R, Zhang A, Wilson LM, et al. (May 2017). "Pharmacotherapy for diabetic
peripheral neuropathy pain and quality of life: A systematic review". Neurology (Systematic Review & Meta-Analysis). 88
(20): 1958–1967. doi:10.1212/WNL.0000000000003882. PMID 28341643. S2CID 40159060.

97. Prevention of DM AND
ITS COMPLICATIONS
1. Early detection
2. Good control of diabetes
3. Prompt treatment of
infections
4. General education

103. Diabetic plate

105. Research on diabetes mellitus
1. Inhalable insulin has been developed. The original
products were withdrawn due to side effects. Afrezza,
under development by the pharmaceuticals company
MannKind Corporation, was approved by the United
States Food and Drug Administration (FDA) for
general sale in June 2014. An advantage to inhaled
insulin is that it may be more convenient and easy to
use.
2. Transdermal insulin in the form of a cream has been
developed and trials are being conducted on people
with type 2 diabetes.
"Inhaled Insulin Clears Hurdle Toward F.D.A. Approval". New York Times. Archived from the original on 7 April 2014. Retrieved 12 April 2014.
"Phosphagenics Initiates Trial of Transdermal Insulin Gel". fdanews.com. Archived from the original on 2016-08-18. Retrieved 2016-07-03.
in-PharmaTechnologist.com. "World's first transdermal insulin shows promise". Archived from the original on 2015-05-01. Retrieved 2016-07-03.

106. 3. C-peptide had shown promising results in
treatment of diabetic complications incidental to
vascular degeneration.
4. Stem cell therapy Clinical trials are under way or
are being populated in preparation for study at
medical centers in Brazil, Iran and the United
States. Current trials involve using the patients'
own stem cells derived from bone marrow and
injected into the degenerated areas in an effort to
regenerate the vascular system.
Garde D (February 24, 2015). "Cebix hangs it up after raising $50M for diabetes drug". FierceBiotech.
Ljubimov A. "Stem Cell Therapy for Diabetic Retinopathy" (PDF). Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, CA, USA
Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Archived from the original (PDF) on 2014-12-30. Retrieved 2014-12-30.

107. External links
1. Diabetes at Curlie
2. American Diabetes Association Archived 2018-12-30 at the
Wayback Machine
3. IDF Diabetes Atlas Archived 2016-03-22 at the Wayback Machine
4. National Diabetes Education Program Archived 2015-11-04 at the
Wayback Machine
5. ADA's Standards of Medical Care in Diabetes 2019 Archived 2020-
08-05 at the Wayback Machine
6. Polonsky KS (October 2012). "The past 200 years in diabetes". The
New England Journal of Medicine. 367 (14): 1332–40.
doi:10.1056/NEJMra1110560. PMID 23034021. S2CID 9456681.
7. "Diabetes". MedlinePlus. U.S. National Library of Medicine.
Archived from the original on 2020-08-10. Retrieved 2020-08-05.

108. THANK YOU
MWEBAZA VICTOR
Ugandan
MBChB 6TH YEAR
mwebazavictor1997@gmail.com
DIABETIS MELLITUS PRESENTATION
7th /March/ 2023