Diabetes Mellitus

Iin Novita Nurhidayati Mahmuda

Internal Medicine
Faculty of medicine
Muhammadiyah University of Surakarta

What is diabetes?

Diabetes mellitus (DM) is a group of diseases

characterized by high levels of blood glucose resulting
from defects in insulin production, insulin action, or
both.

The term diabetes mellitus describes a metabolic

disorder of multiple aetiology characterized by chronic
hyperglycaemia with disturbances of carbohydrate, fat
and protein metabolism resulting from defects in
insulin secretion, insulin action, or both.

The effects of diabetes mellitus include longterm

damage, dysfunction and failure of various organs.

Diabetes

Diabetes mellitus may present with characteristic

symptoms such as thirst, polyuria, blurring of vision,
and weight loss.

In its most severe forms, ketoacidosis or a nonketotic

hyperosmolar state may develop and lead to stupor,
coma and, in absence of effective treatment, death.

Often symptoms are not severe, or may be absent,

and consequently hyperglycaemia sufficient to cause
pathological and functional changes may be present
for a long time before the diagnosis is made.

Diabetes Long-term Effects

The longterm effects of diabetes mellitus include

progressive development of the specific
complications of retinopathy with potential
blindness, nephropathy that may lead to renal
failure, and/or neuropathy with risk of foot ulcers,
amputation, Charcot joints, and features of
autonomic dysfunction, including sexual
dysfunction.

People with diabetes are at increased risk of

cardiovascular, peripheral vascular and
cerebrovascular disease.

Burden of Diabetes

The development of diabetes is projected to reach pandemic

proportions over the next10-20 years.

International Diabetes Federation (IDF) data indicate that by

the year 2025, the number of people affected will reach 333
million 90% of these people will have Type 2 diabetes.

In most Western societies, the overall prevalence has

reached 4-6%, and is as high as 10-12% among 60-70-yearold people.

The annual health costs caused by diabetes and its

complications account for around 6-12% of all health-care
expenditure.

Types of Diabetes
Type

1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Gestational Diabetes
Other types:
LADA (Latent Autoimun Diabetes of Adult )
MODY (maturity-onset diabetes of

youth)
Secondary Diabetes Mellitus

Type 1 diabetes

Was previously called insulin-dependent diabetes

mellitus (IDDM) or juvenile-onset diabetes.

Type 1 diabetes develops when the bodys immune

system destroys pancreatic beta cells, the only cells in
the body that make the hormone insulin that regulates
blood glucose.

This form of diabetes usually strikes children and young

adults, although disease onset can occur at any age.

Type 1 diabetes may account for 5% to 10% of all

diagnosed cases of diabetes.

Risk factors for type 1 diabetes may include

autoimmune, genetic, and environmental factors.

Type 2 diabetes

Was previously called non-insulin-dependent diabetes

mellitus (NIDDM) or adult-onset diabetes.

Type 2 diabetes may account for about 90% to 95% of all

diagnosed cases of diabetes.

It usually begins as insulin resistance, a disorder in which the

cells do not use insulin properly. As the need for insulin rises,
the pancreas gradually loses its ability to produce insulin.

Type 2 diabetes is associated with older age, obesity, family

history of diabetes, history of gestational diabetes, impaired
glucose metabolism, physical inactivity, and race/ethnicity.

African Americans, Hispanic/Latino Americans, American

Indians, and some Asian Americans and Native Hawaiians or
Other Pacific Islanders are at particularly high risk for type 2
diabetes.

Type 2 diabetes is increasingly being diagnosed in children

and adolescents.

Gestational diabetes

A form of glucose intolerance that is diagnosed in some

women during pregnancy.

Gestational diabetes occurs more frequently among

African Americans, Hispanic/Latino Americans, and
American Indians. It is also more common among obese
women and women with a family history of diabetes.

During pregnancy, gestational diabetes requires

treatment to normalize maternal blood glucose levels to
avoid complications in the infant.

After pregnancy, 5% to 10% of women with gestational

diabetes are found to have type 2 diabetes.

Women who have had gestational diabetes have a 20%

to 50% chance of developing diabetes in the next 5-10
years.

Other types of DM

Other specific types of diabetes result

from specific genetic conditions (such
as maturity-onset diabetes of youth),
surgery, drugs, malnutrition,
infections, and other illnesses.

Such types of diabetes may account for

1% to 5% of all diagnosed cases of
diabetes.

LADA

Latent Autoimmune Diabetes in Adults (LADA)

is a form of autoimmune (type1 diabetes)
which is diagnosed in individuals who are older
than the usual age of onset of type 1 diabetes.
Alternate terms that have been used for
"LADA" include Late-onset Autoimmune
Diabetes of Adulthood, "Slow Onset Type 1"
diabetes, and sometimes also "Type 1.5
Often, patients with LADA are mistakenly
thought to have type2 diabetes, based on
their age at the time of diagnosis.

LADA (cont.)

LADA (cont.)

About 80% of adults apparently with

recently diagnosed Type 2 diabetes but with
GAD auto-antibodies (i.e. LADA) progress to
insulin requirement within 6 years.

The potential value of identifying this group

at high risk of progression to insulin
dependence includes:
the avoidance of using metformin treatment
the early introduction of insulin therapy

MODY

MODY Maturity Onset Diabetes of the Young

MODY is a monogenic form of diabetes with an autosomal

dominant mode of inheritance:
Mutations in any one of several transcription factors or in the enzyme
glucokinase lead to insufficient insulin release from pancreatic -cells,
causing MODY.
Different subtypes of MODY are identified based on the mutated gene.

Originally, diagnosis of MODY was based on presence of nonketotic hyperglycemia in adolescents or young adults in
conjunction with a family history of diabetes.

However, genetic testing has shown that MODY can occur at

any age and that a family history of diabetes is not always
obvious.

MODY (cont.)

MODY (cont.)

Within MODY, the different subtypes can essentially

be divided into 2 distinct groups: glucokinase MODY
and transcription factor MODY, distinguished by
characteristic phenotypic features and pattern on
oral glucose tolerance testing.

Glucokinase MODY requires no treatment, while

transcription factor MODY (i.e. Hepatocyte nuclear
factor -1alpha) requires low-dose sulfonylurea
therapy and PNDM (caused by Kir6.2 mutation)
requires high-dose sulfonylurea therapy.

Secondary DM
Secondary causes of Diabetes mellitus include:

Acromegaly,
Cushing syndrome,
Thyrotoxicosis,
Pheochromocytoma
Chronic pancreatitis,
Cancer
Drug induced hyperglycemia:
Atypical Antipsychotics - Alter receptor binding characteristics, leading to increased insulin
resistance.
Beta-blockers - Inhibit insulin secretion.
Calcium Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic
calcium release.
Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.
Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium channels.
Naicin - They cause increased insulin resistance due to increased free fatty acid
mobilization.
Phenothiazines - Inhibit insulin secretion.
Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause increased
insulin resistance due to increased free fatty acid mobilization.

Prediabetes: Impaired glucose tolerance and

impaired fasting glucose
Prediabetes

is a term used to distinguish people who are

at increased risk of developing diabetes. People with
prediabetes have impaired fasting glucose (IFG) or
impaired glucose tolerance (IGT). Some people may have
both IFG and IGT.

IFG

is a condition in which the fasting blood sugar level is

elevated (100 to 125 milligrams per decilitre or mg/dL)
after an overnight fast but is not high enough to be
classified as diabetes.

IGT

is a condition in which the blood sugar level is

elevated (140 to 199 mg/dL after a 2-hour oral glucose
tolerance test), but is not high enough to be classified as
diabetes.

Prediabetes: Impaired glucose

tolerance and impaired fasting glucose
(cont.)

Progression to diabetes among those with

prediabetes is not inevitable. Studies suggest
that weight loss and increased physical activity
among people with prediabetes prevent or delay
diabetes and may return blood glucose levels to
normal.

People with prediabetes are already at increased

risk for other adverse health outcomes such as
heart disease and stroke.

Diagnosis of Diabetes
Mellitus

Values of Diagnosis of Diabetes

Mellitus

Principal Management in
Type 2 Diabetes Mellitus*
4
3
PHARMACOLOGIC
TREATMENT

1
MEDICAL NUTRITION
THERAPY

PHYSICAL
ACTIVITY

* Konsensus Pengelolaan Diabetes Melitus di Indonesia, Perkeni 2011.

EDUCATION

A. Diet

Diet is a basic part of management in every

case. Treatment cannot be effective unless
adequate attention is given to ensuring
appropriate nutrition.

Dietary treatment should aim at:

ensuring weight control
providing nutritional requirements
allowing good glycaemic control with blood glucose
levels as close to normal as possible
correcting any associated blood lipid abnormalities

A. Diet (cont.)
The following principles are recommended as dietary
guidelines for people with diabetes:

Dietary fat should provide 25-35% of total intake of calories but

saturated fat intake should not exceed 10% of total energy.
Cholesterol consumption should be restricted and limited to 300 mg
or less daily.

Protein intake can range between 10-15% total energy (0.8-1 g/kg
of desirable body weight). Requirements increase for children and
during pregnancy. Protein should be derived from both animal and
vegetable sources.

Carbohydrates provide 50-60% of total caloric content of the diet.

Carbohydrates should be complex and high in fibre.

Excessive salt intake is to be avoided. It should be particularly

restricted in people with hypertension and those with nephropathy.

Exercise

Physical activity promotes weight reduction and

improves insulin sensitivity, thus lowering blood
glucose levels.

Together with dietary treatment, a programme of

regular physical activity and exercise should be
considered for each person. Such a programme
must be tailored to the individuals health status
and fitness.

People should, however, be educated about the

potential risk of hypoglycaemia and how to avoid it.

B. Oral Anti-Diabetic Agents

There are currently four classes of oral antidiabetic agents:

i. Biguanides
ii. Insulin Secretagogues Sulphonylureas
iii. Insulin Secretagogues Nonsulphonylureas (Glinid)
iv. -glucosidase inhibitors
v. Thiazolidinediones (TZDs)
vi. DPP IV Inhibitor

DiabetesCare,Diabetolo
[Epubahead

ntihyperglycemic Therapy: General Recommendations

DiabetesCare,Diabetolo
[Epubahead

ntihyperglycemic Therapy: General Recommendations

DiabetesCare,Diabetolo
[Epubahead

ntihyperglycemic Therapy: General Recommendations

DiabetesCare,Diabetologia.
19April2012[Epubaheadofprint]

B.1 Oral Agent Monotherapy

(cont.)
As first line therapy:

Obese type 2 patients, consider use of metformin, acarbose or TZD.

Non-obese type 2 patients, consider the use of metformin or insulin

secretagogues

Metformin is the drug of choice in overweight/obese patients. TZDs

and acarbose are acceptable alternatives in those who are
intolerant to metformin.

If monotherapy fails, a combination of TZDs, acarbose and

metformin is recommended. If targets are still not achieved, insulin
secretagogues may be added

B.2 Combination Oral Agents

Combination oral agents is indicated in:

Newly diagnosed symptomatic patients with

HbA1c >10

Patients who are not reaching targets after

3 months on monotherapy

B.3 Combination Oral Agents and Insulin

If targets have not been reached after optimal dose of combination

therapy for 3 months, consider adding intermediate-acting/longacting insulin (BIDS).

Combination of insulin+ oral anti-diabetic agents (BIDS) has been

shown to improve glycaemic control in those not achieving target
despite maximal combination oral anti-diabetic agents.

Combining insulin and the following oral anti-diabetic agents has

been shown to be effective in people with type 2 diabetes:
Biguanide (metformin)
Insulin secretagogues (sulphonylureas)
Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an
approved indication)
-glucosidase inhibitor (acarbose)

Insulin dose can be increased until target FPG is achieved.

Oral Hypoglycaemic Medications

General Guidelines for Use of Oral Anti-Diabetic Agent

inDiabetes

In elderly non-obese patients, short acting insulin secretagogues can be

started but long acting Sulphonylureas are to be avoided. Renal function
should be monitored.

Oral anti-diabetic agent s are not recommended for diabetes in

pregnancy

Oral anti-diabetic agents are usually not the first line therapy in
diabetes diagnosed during stress, such as infections. Insulin therapy is
recommended for both the above

Targets for control are applicable for all age groups. However, in
patients with co-morbidities, targets are individualized

When indicated, start with a minimal dose of oral anti-diabetic agent,

while reemphasizing diet and physical activity. An appropriate duration
of time (2-16 weeks depending on agents used) between increments
should be given to allow achievement of steady state blood glucose
control

Terapi insulin
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

Type 1 diabetes
Uncontrolled type 2 diabetes.
Gestasional diabetes
Liver/renal insufficiency.
Acute infection (celulitis, gangren), TBC,
stroke/AMI.
KAD/HHS
Major surgery
Under weight, MRDM
Graves disease
Cancer
Corticosteroid treatment

Insulin regimens

The majority of patients will require more than one daily injection if
good glycaemic control is to be achieved. However, a once-daily
injection of an intermediate acting preparation may be effectively
used in some patients.

Twice-daily mixtures of short- and intermediate-acting insulin is a

commonly used regimen.

In some cases, a mixture of short- and intermediate-acting

insulin may be given in the morning. Further doses of short-acting
insulin are given before lunch and the evening meal and an evening
dose of intermediate-acting insulin is given at bedtime.

Other regimens based on the same principles may be used.

A regimen of multiple injections of short-acting insulin before the

main meals, with an appropriate dose of an intermediate-acting
insulin given at bedtime, may be used, particularly when strict
glycaemic control is mandatory.

Overview of Insulin and Action

Self-Care

Patients should be educated to practice self-care. This

allows the patient to assume responsibility and control
of his / her own diabetes management. Self-care
should include:

Blood glucose monitoring

Body weight monitoring
Foot-care
Personal hygiene
Healthy lifestyle/diet or physical activity
Identify targets for control
Stopping smoking

Komplikasi Diabetes
hipoglikemi
Komplikasi akut
hiperglikemi

Keto-asidosis diabetik
Koma hiperglikemi
hiperosmoler non-ketotik

mikroangiopathy

Komplikasi kronis
makroangiopathy

Microangiopathy
Diabetic
Retinopathy
Leading cause
of blindness
in adults1,2

Diabetic
Nephropathy
Leading cause of
end-stage
renal disease3,4

Diabetic
Neuropathy

Macroangiopathy
Stroke
2- to 4-fold increase
in
cardiovascular
mortality and stroke5

Cardiovascular
Disease
8/10 individuals with
diabetes die from CV
events6

Peripheral
Arterial
Disease

UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:111. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99S102. 3The Hypertension in Diabetes
Study Group. J Hypertens 1993; 11:309317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94S98. 5Kannel WB, et al. Am Heart J 1990; 120:672676.
6
Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7Kings Fund. Counting the cost.
The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78S79.
1

Chronic complications treatment

and management
Glycemic control
Blood pressure control
Lipid control
Others: healthy lifestyle and diet
scheduling
Some distinctive methods:

Retinopathy with photo coagulation

Nephropathy with dialysis: hemodialysis or
peritonial
CHD with stent installment
Peripheral vascular disease with metabolic and
infection control, foot rest
Neuropathy symptomatis

Complications:
Macrovascular
DM increases the risk of coronary artery
disease, stroke, and peripheral vascular
disease 2 to 4 times.
Although controlling the glucose may be
important early in the disease, controlling
the BP and lipids, avoiding smoking, and
taking ASA when indicated are much more
important for prevention.

Complications:
Neuropathy
Present in 60 - 70% of diabetics.
Symmetric distal polyneuropathy is the
most common type,
and leads to Charcot joints, dislocations,
fractures, ulcers, infections, and
amputations.
Prevention/Treatment: Control glucose,
teach good foot care, do a foot exam
yearly, refer to Podiatry if neuropathy or
its complications are present, and control
pain: tricyclics, topicals and
anticonvulsants.

Complications: Microvascular
Nephropathy
Present in 20 - 40% of diabetics.
Prevention/Treatment: Maintain BP
140/80, keep glucose at goal, and check
urine albumin/creatinine ratio yearly. Use
ACE inhibitor or ARB to treat BP.

Complications: Microvascular
Retinopathy
Present in 40 - 45% of diabetics.
Prevention/Treatment: Control BP and
glucose to previously mentioned goals, and
refer to Ophthalmology for yearly screening
exam/treatment.

Kriteria pengendalian

Are we doing a good job with

treatment?
Only 52.5% of diabetics
7%.
Only 51.1% of diabetics
130/80.
Only 56.2% of diabetics
cholesterol
< 100 mg/dl.
Only 18.8% of diabetics
goals!

have a HBA1C <

have a BP <
have an LDL

are meeting all 3

Why do we do such a poor

job?
Patient reasons: Cost, side effects, fear of
side effects, fear of injections, and denial of
disease.
Physician reasons: Clinical inertia - not
enough time, not enough resources,
concern about cost and pill burden, care
directed at acute problems, and lack of
knowledge of goals.

Health Maintenance

Pneumovax once, then repeat after age 65.

Hepatitis B vaccine now recommended by the
ACIP/CDC.
All other vaccinations as are appropriate for age.
Routine dental exams.
Contraception counseling for women of child
bearing age.
Age appropriate cancer screening only (the
meaning of the increased risk of liver, pancreas,
uterus, colon, breast and bladder cancers, and the
decreased risk of prostate cancer, is unclear).

First Case

A 61 year old woman comes to see you for a

checkup after being told her BP elevated. She is
asymptomatic. She has not seen a doctor in
many years, and is on no prescription or other
medications. She does not exercise or eat a
healthy diet, and she does not smoke or drink.
She has no health insurance. Her mother and 2
sisters have DM and HT.
On PE her BP is 155/95, BMI of 40. Otherwise, her
PE is normal.
What labs would you order at this point?

Who should be screened for

DM?

Everyone age 45 and over.

Everyone under 45 with a BMI 25 kg/m and one

other risk factor for DM:
Family history in a 1st degree relative.
Race/ethnicity of Native American, African American,
Latino, Asian American, or Pacific Islander.
History of gestational DM or delivery of a baby 9 lbs.
Polycystic ovary syndrome, HTN, lipid disorder,
acanthosis nigricans, CVD or sedentary lifestyle.

If screening is normal, it should be repeated every

3 years.

ADA.Diabetes Care,2014;37(Suppl 1):S5-S80.

First Case (cont)

Lab Results
Fasting glucose: 150 mg/dl
Chol: 240 mg/dl

TG: 250 mg/dl

HDL: 36 mg/dl

LDL: 154 mg/dl

HBA1C: 8.8%

What diagnoses would you give her at this time?

How do you diagnose DM?

Fasting plasma glucose 126 mg/dl, or
2 hour plasma glucose 200 mg/dl during
an oral glucose tolerance test, or
Symptoms of hyperglycemia and a
random plasma glucose 200 mg/dl, or
HBA1C 6.5%.

All should be repeated before making the

diagnosis, unless 2 different tests are both
consistent with DM.

ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.

How do you diagnose

pre-diabetes?

Impaired Fasting Glucose (IFG): fasting plasma

glucose 100 mg/dl and 125 mg/dl, or
Impaired Glucose Tolerance (IGT): 2 hour plasma
glucose 140 mg/dl and 200 mg/dl during an
oral glucose tolerance test, or
HBA1C 5.7 - 6.4%.

All should be repeated before making the

diagnosis.

ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.

Why and how should we treat

pre-diabetes?

It confers an increased risk of CVD, and without

intervention, most will develop DM within 10 years.
Aim for a weight loss of 5 - 10% and at least 150 minutes of
moderate activity per week.
Consider metformin for those with a BMI > 35, those who
are younger than 60, and women with prior gestational
diabetes.

Monitor at least yearly.

ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.

First Case (cont)

What treatment would you institute for this

patient with newly diagnosed DM and a
HBA1C of 8.8%?

How do you manage DM?

Referral to a Diabetes Education Program to

assist in education on Medical Nutrition Therapy
(MNT), exercise, and all aspects of the disease,
including treatment, self monitoring,
complications, and the concept that it is a
progressive disease leading to insulin therapy in
most patients.
Medication for glycemic control.
Monitoring for complications.
Treatment of HTN.
Smoking cessation.
Consider referral for bariatric surgery if BMI 35.
ADA.Diabetes Care.2014;37(Suppl 1):S5-S80.

What are the glycemic

goals?
HBA1C < 7%.

Fasting/Preprandial/Bedtime (AC and HS) capillary

blood glucose (CBG) 70 - 130 mg/dl.
Postprandial CBG 1 - 2 hours after starting a meal
< 180 mg/dl.
Goal is to achieve glycemic target without causing
hypoglycemia.
Reaching goal glycemia has been clearly shown to
prevent microvascular complications; its effect
on the prevention of macrovascular
complications is less clear, but seems to be most
important when attained early in the course of
DM. Control of BP & lipids, use of ASA, and
smoking cessation are essential in preventing
CVD.

ADA.Diabetes Care, 2014;37 (Suppl 1):S5-S80.

Does tight glycemic control

prevent macrovascular disease?
Based upon the findings of the UKPDS, ACCORD, ADVANCE
and VADT trials, the ADA, AHA, and ACC issued a joint
statement supporting the individualization of treatment
goals, and stressing the importance of aggressive
treatment and control early in the course of the disease.

Patients with a history of severe hypoglycemia, limited life

expectancy, advanced microvascular and macrovascular
complications, extensive comorbidities, or longstanding
difficult to control DM, may reasonably have a HBA1C goal
that is > 7%.

Patients with a shorter duration of DM, a long life

expectancy, and no significant complications, may
reasonably have a HBA1C goal that is lower, < 7% or even
< 6.5%.

Skyler etal.Diabetes Care.2009;32:187-192.

How do you choose medication

for glycemic control?

Choose based upon potency, safety, side

effects, ease of use, effect on other risk
factors, and cost.
There is no good data yet showing that
one class of medication prevents
complications better than another, other
than through the level of glycemic control
and effects on other risk factors.

Medications for DM:

Biguanides - Metformin (Glucophage) - decrease hepatic

glucose output - weight neutral or mild loss, no hypoglycemia,

cheap - GI side effects, contraindicated in CRF and unstable CHF
because of risk of lactic acidosis, B12 deficiency.
Sulfonylureas - Glipizide (Glucotrol), glimeperide (Amaryl) enhance insulin secretion - cheap - weight gain, hypoglycemia.
Insulins - Lispro (Humalog), aspart (Novolog), glulisine (Apidra);
Regular; NPH; glargine (Lantus), detemir (Levemir); and fixed
combinations - no dose limit, NPH and Regular are cheap, improve
lipids - injections, weight gain, hypoglycemia, analogs are
expensive.

Medications for DM:

(cont)
Thiazolidinediones (TZDs or Glitazones) - Pioglitazone
(Actos) - increase sensitivity to insulin - improve lipids, potential
decrease in MI, no hypoglycemia - fluid retention, weight gain,
CHF, fractures, bladder cancer (taken off of market in France and
Germany).
* DPP-4 Inhibitors - Sitagliptin (Januvia), saxagliptan
(Onglyza), linagliptin (Tradjenta), alogliptin (Nesina) - increase
glucose-mediated insulin secretion, suppress glucagon secretion weight neutral, no hypoglycemia - expensive, ?effects on immune
system/pancreatitis/pancreatic cancer, long term effects not
known.
GLP-1 Agonists (Incretin Mimetics) - Exenatide (Byetta,
Bydureon), liraglutide (Victoza) - potentiate glucose-stimulated
insulin secretion, suppress glucagon secretion, slow gastric
motility - weight loss, ?delay/prevention of beta cell failure, no
hypoglycemia - injections, expensive, GI side effects, ?
pancreatitis/pancreatic cancer, ?medullary CA of the thyroid, long
term effects not known.

Other Medications for DM :

-Glucosidase Inhibitors - Acarbose (Precose), miglitol (Glyset) reduce the rate of digestion of polysaccharides - weight neutral, no
hypoglycemia - severe GI side effects, expensive, three times daily.
Glinides - Nateglinide (Starlix), repaglinide (Prandin) - stimulate insulin
secretion - weight gain, three times daily, expensive, hypoglycemia.

How potent are these medications?

*If initial HBA1C is 9%, use 2 medications. If initial glucose is 300350mg/dl, or HBA1C is 10-12%, use insulin.

Medication
Biguanides
Sulfonylureas
Insulin
TZDs
DPP - 4 Inhibitors
GLP - 1 Agonists
- Glucosidase Inhibitors
Glinides

Expected decrease in
HBA1C
1.0 - 2.0
1.0 - 2.0
No limit
0.5 - 1.4
0.5 - 0.8
0.5 - 1.0
0.5 - 0.8
0.5 - 1.5

First Case (cont)

She was referred to the Diabetes Center for MNT

and general teaching.
She was started on metformin 500 mg twice
daily, and was told to increase to 1000 mg twice
daily after 2 weeks.
She was referred to Ophthalmology.
She was scheduled to return to clinic in 3 months
for follow-up, with a HBA1C and a urine
microalbumin/creatinine one week before her
appointment.
Should any other medications be prescribed
at this time?

What other disorders need

treatment in patients with DM?

In addition to treating the glucose, we must

also treat the HTN, lipid abnormalities
ACE Inhibitor (or ARB) for HTN, with a goal BP of 140/80 (per
ACCORD tight control of HTN arm), although lower may be
appropriate for some patients. Take at least one medication at
bedtime. (*JNC 8 and ASH/ISH guidelines differ.)
Statin if above goal. Statin if overt CVD, or over age 40 with one
or more other risk factors, regardless of baseline LDL. Goal LDL
less than 100 mg/dl, and less than 70 mg/dl for overt CVD (or 30 40% below baseline). Treat TG if > 400 mg/dl. (*ACC/AHA
guidelines use intensity of therapy rather than goals.)
Low dose ASA if overt CVD. Low dose ASA for men over 50 and
women over 60 who have one or more other risk factors.
Clopidogrel (Plavix) should be used in the case of ASA allergy.

ADA.Diabetes Care,2014;37(Suppl 1):S5-S80.

First Case (cont)

Lisinopril 20 mg daily was added, and a

BMP was ordered for 2 weeks.

Atorvastatin 40 mg daily was added, and

lipids were ordered for one week before her
3 month appointment.

ASA 80 mg daily was added.

How do you monitor

therapy?
HBA1C level every 3 months if
uncontrolled or if therapy is changed,
otherwise every 6 months.
Self monitoring of blood glucose is
definitely indicated for patients on multiple
daily doses of insulin, and may be
indicated for patients on one dose of
insulin daily, or on non insulin therapy
particularly if there is a risk of
hypoglycemia.

First Case (cont)

She returns to clinic in 3 months. She has
lost 5 kg.
HBA1C is 6.1%, BP is 145/85, electrolytes
were normal, Chol is 180 mg/dl, LDL is 68
mg/dl, HDL is 40 mg/dl, TG is 210 mg/dl,
and she has no albuminuria.

HCTZ 25 mg daily is added.

You are satisfied with her DM control.
She is scheduled to return to clinic in 3
months with a BMP.

First Case (cont)

She unfortunately does not return to see
you for one year, but she has continued to
take her medications as prescribed. She
has gained 15 kg.
Now her BP is 120/75, and HBA1C is
7.8%.

What medication adjustments, if any,

do you make at this time?

First Case (cont)

You add glipizide ER 10 mg daily.
You send her back to diabetes education to
reinforce diet and exercise.
She returns to clinic in 3 months with a
HBA1C of 7.4%, an LDL at goal, and no
albuminuria. She has lost 10 kg.
What medication adjustments, if any,
do you make at this time?

First Case (cont)

You add long acting insulin 10 units once
daily. (She knows how to use insulin from
giving it to her mother.)
She returns to clinic in 3 months with a
HBA1C of 6.0%. She has lost another 5
kg.
You are happy with her control, and
schedule her to return to clinic in 6
months with a HBA1C before.

Second Case

This is a 69 year old woman who has been followed

elsewhere for DM for 15 years, HTN for 8 years,
osteoporosis for 3 years, and hyperlipidemia for 5 years.
She has had several episodes of hypoglycemia recently,
usually after being late for a meal, and once in the middle
of the night requiring an ER visit after a fall. She does not
smoke or drink, lives alone, and has no family in town.
Meds: Glybenclamide 5 mg daily, metformin 1000 mg twice
daily, ramipril 10 mg daily, simvastatin 40 mg daily, ASA
81mg daily, alendronate 70 mg weekly, and calcium with
vitamin D.

Second Case (cont)

BP 128/78, BMI 35, fundi are normal, she has

decreased sensation to filament exam on both
feet, and the remainder of the PE is normal.
She checks her CBGs AC breakfast and dinner,
and they are 75-110 AC breakfast and 200 post
dinner.
HBA1C is 7.9%, but the remainder of her labs are
normal.
What medication adjustments, if any, do
you make?

Second Case (cont)

Glybenclamide stop
She was referred to the Diabetes Educator to
learn injection insulin rapid acting three times
daily reinforce prior teaching.
Follow-up HBA1C is 6.8%, her CBGs are at goal,
and she has had no further episodes of
hypoglycemia.
She has also lost 10 kg.

Third Case

A 42 year old man with HTN, hyperlipidemia and

an ischemic cardiomyopathy with an EF of 25%
and severe SOB on minimal exertion, is referred
to you by his cardiologist for management of
fairly newly diagnosed DM.
Meds: Metformin 500 mg twice daily, pioglitazone
15 mg daily, carvedilol 12,5 mg twice daily,
furosemide 40 mg daily, lisinopril 20 mg daily,
rosuvastatin 20 mg daily, and ASA 80 mg daily.

Third Case (cont)

BP 110/60, Wt 240 lbs, BMI 35, fundi difficult to

visualize, elevated neck veins, S3 gallop,
holosystolic murmur, 1+ edema, but foot exam
was otherwise normal.
He brings in a copy of recent labs:
HBA1C 10.2%, FBS 252 mg/dl, Crt 1.8 mg/dl, and
Ur Alb/Crt 50 mg/g (nl < 30).
What medication adjustments, if any, would
you make?

Third Case (cont)

Metformin and pioglitazone were both

discontinued .
Insulin glargine 30 units daily was started, and he
was sent to the Diabetes Educator to learn
injection, self monitoring techniques, and self
titration of insulin to reach a target FBS.
He was also referred to Ophthalmology.
He returned to clinic in 3 months on 45 units of
insulin glargine daily with a glucose log showing
fasting CBGs at goal, but a HBA1C of 7.9%.

Third Case (cont)

He then began checking AC and PC CBGs.
The AC breakfast and dinner CBGs were at
goal, but the AC lunch and PC CBGs were
high, prompting the addition of 3 units of
insulin lispro before breakfast and dinner.
He was instructed on self titration of the
insulin lispro, which was raised to 6 units at
both times, resulting in AC and PC CBGs
that were all at goal.
A follow up HBA1C in 3 months was 6.8%.