Diabetes Mellitus

Objectives

Introduction & Epidemiology

Definition & Types
Diagnosis
Primary & Secondary Prevention
Comprehensive Medical Evaluation & Assessment
Treatment
Comorbidities
Special Groups
Complications
Cardiovascular Risk Charts
Diabetic Emergencies
Introduction & Epidemiology (WHO 2021)

Diabetes is a chronic, metabolic disease characterized by elevated

levels of blood glucose, which leads over time to serious damage to
the heart, blood vessels, eyes, kidneys and nerves.

The most common is type 2 diabetes, usually in adults, which

occurs when the body becomes resistant to insulin or doesn't make
enough insulin. In the past three decades the prevalence of type 2
diabetes has risen dramatically in countries of all income levels.

Type 1 diabetes, once known as juvenile diabetes or insulin-

dependent diabetes, is a chronic condition in which the pancreas
produces little or no insulin by itself.
For people living with diabetes, access to affordable treatment,
including insulin, is critical to their survival. There is a globally agreed
target to halt the rise in diabetes and obesity by 2025. 

About 422 million people worldwide have diabetes, the majority living
in low-and middle income countries, and 1.5 million deaths are directly
attributed to diabetes each year.

Both the number of cases and the prevalence of diabetes have been
steadily increasing over the past few decades. 
In 2014, 8.5% of adults aged 18 years and older had diabetes.

In 2019, diabetes was the direct cause of 1.5 million deaths and 48% of all
deaths due to diabetes occurred before the age of 70 years.

Between 2000 and 2016, there was a 5% increase in premature mortality

rates (i.e. before the age of 70) from diabetes. In high-income countries
the premature mortality rate due to diabetes decreased from 2000 to 2010
but then increased in 2010-2016. In lower-middle-income countries, the
premature mortality rate due to diabetes increased across both periods. 
Gaza Statistics (MoH 2020)

Incidence rate 110.2/100.000.

Prevalence: 63.627 cases, 57% were female, 43% were male.
82.5% of all cases have their files at UNRWA clinics.
Prevalence rate: 3.1/100.
Prevalence rate among females: 3.5/100.
Prevalence rate among males: 2.6/100.
Prevalence rate in people ≥18: 6.2/100 (International statistics- Europe &
China 4.7-11.1%).
Mortality rate among persons with diabetes: 2/1000, 49% were female.
Definition of Diabetes

Diabetes is a group of metabolic diseases characterized by

hyperglycemia resulting from defects in insulin secretion, insulin
action, or both.

The chronic hyperglycemia of diabetes is associated with long-

term damage, dysfunction, and failure of different organs,
especially the eyes, kidneys, nerves, heart, and blood vessels.
Classification & Diagnosis

Type 1 diabetes: (due to autoimmune b-cell destruction, usually leading to

absolute insulin deficiency including latent autoimmune diabetes of adulthood)

Type 2 diabetes: (due to a progressive loss of b-cell insulin secretion frequently

on the background of insulin resistance)

Gestational diabetes mellitus (GDM): (diabetes diagnosed in the 2nd or 3rd

trimester of pregnancy that was not clearly overt diabetes prior to gestation)
Specific Types
Monogenic diabetes syndromes:
 Neonatal diabetes
 Maturity-onset diabetes of the young
 Diseases of the exocrine pancreas (Cystic fibrosis and pancreatitis)

Drug- or chemical-induced diabetes:

 Glucocorticoid use
 Treatment of HIV/AIDS
 After organ transplantation
Classification of diabetes type is not always straightforward at
presentation, and misdiagnosis may occur.

Children with type 1 diabetes typically present with

polyuria/polydipsia, and approximately half present with
diabetic ketoacidosis (DKA).

Adults with type 1 diabetes may not present with classic symptoms
and may have a temporary remission from the need for insulin.
 Type 1 Diabetes

Clinical Clues for Diagnosis

Presentation Likely Diagnosis

Lean individual with symptoms but without a

Type 1 Diabetes
first-degree relative with diabetes

Type 2 Diabetes
Overweight individual with symptoms and family
Type 1 Diabetes is a differential
history of Type 2 diabetes
diagnosis

Potential for type 1 exists in individuals who phenotypically appear to have type 2
If hyperglycemia persists after treatment with noninsulin agents, consider type 1

 Pancreatic antibodies are characteristics of type 1:

 GAD antibodies (GADA)
 Islet cell antibodies (ICA)
 Insulin autoantibodies (IAA)
 Protein tyrosine phosphatase antibodies (ICA512)
 Zinc transporter protein (ZnT8)
Risk factors for Diabetes

Genetic factors
Environmental factors
Excessive caloric intake
Obesity
Lack of exercise
Hypertension and prehypertension
Low birth weight
Signs & Symptoms of Diabetes

3 Ps (Polydipsia, Polyuria, Polyphagia)

Fatigue

Weight loss

Recurrent infections (Gingivitis, vaginitis, UTI , skin infections, etc.)

Paresthesia

Blurred vision

Some people with diabetes don’t have any of these signs or symptoms.
Definition of Prediabetes
“Prediabetes” is the term used for individuals whose glucose levels do
not meet the criteria for diabetes but are too high to be considered
normal.

Patients with prediabetes are defined by the presence of IFG and/or

IGT and/or A1C 5.7–6.4%.

Prediabetes has an an increased risk for diabetes and CVD.

Prediabetes is associated with obesity (especially abdominal or

visceral obesity), dyslipidemia with high triglycerides and/or low HDL
cholesterol, and hypertension.
Diagnostic Tests for Prediabetes and
Diabetes
 Criteria for the Screening and Diagnosis of Prediabetes and Diabetes
Prediabetes Diabetes
Fasting plasma In the absence of unequivocal hyperglycemia,
diagnosis requires two abnormal test results
glucose* 100–125 mg/dL ≥126 mg/dL from the same sample or in two separate
samples
In the absence of unequivocal hyperglycemia,
diagnosis requires two abnormal test results
A1C 5.7–6.4% ≥6.5% from the same sample or in two separate
samples

2-hour plasma In the absence of unequivocal hyperglycemia,

diagnosis requires two abnormal test results
glucose during 75-g 140–199 mg/dL ≥200 mg/dL from the same sample or in two separate
OGTT samples
Only diagnostic in a patient with classic
Random plasma
— ≥200 mg/dL symptoms of hyperglycemia or hyperglycemic
glucose crisis.
* Fasting: No calorie intake for 8 hours. Water and medications (Antihypertensives, antianginal drugs,
etc...) can be taken.
Primary Prevention
Lifestyle Behavior Change for Diabetes
Prevention
Refer adults with overweight/obesity at high risk of type 2
diabetes to an intensive lifestyle behavior change program:

achieve and maintain 7% loss of initial body weight

increase moderate-intensity physical activity to at least 150
min/week

Intensive lifestyle intervention could reduce the risk of incident

type 2 diabetes by 58% over 3 years.
Pharmacologic Interventions

Metformin for prevention of type 2 diabetes in prediabetes (ADA

2022):
Adults aged 25–59 years with BMI ≥35 kg/m2, higher fasting,
plasma glucose (e.g., ≥110 mg/dL), and higher A1C (e.g., ≥6.0%)
Prior GDM

Long-term use of metformin may be associated with vitamin B12

deficiency; consider periodic measurement of vitamin B12 levels,
especially in patients with anemia or peripheral neuropathy.
Screening
Definition of Screening

Testing for diabetes or prediabetes in asymptomatic people.

Screening Groups

1. Low-risk Groups:

Testing should begin at age 45 years (ADA 2021).

Testing should begin at age 35 years (ADA 2022).
2. High-risk Groups:

Adults (>18 years) with overweight or obesity (BMI ≥25 kg/m 2) who
have one or more of the following risk factors:

Having a first-degree relative with diabetes

History of CVD
History of hypertension (≥140/90 mmHg or on therapy)
History of dyslipedemia (HDL <35 and/or triglycerides >250 mg/dL
History of gestational diabetes or preeclampsia
Women with polycystic ovary syndrome
Physical inactivity
Other clinical conditions associated with insulin resistance (e.g.,, acanthosis
nigricans)
3. Children and Adolescents (10-18 years):

Risk-based screening should be considered after the onset of puberty

or after 10 years of age, whichever occurs earlier, in children and
adolescents with overweight (BMI ≥ 85th percentile) or obesity (BMI
≥ 95thpercentile) and who have additional risk factors for diabetes:

Maternal history of diabetes or GDM during the child’s gestation

Family history of type 2 diabetes in first- or second-degree relative
Signs of insulin resistance or conditions associated with insulin resistance
(acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome,
or small-for-gestational-age birth weight)
 Gestational Diabetes Mellitus (GDM)
Diagnosis of Gestational Diabetes Mellitus (GDM)
The diagnosis of gestational diabetes mellitus between 24th – 28th week of gestational age should be based on any on of the following
values:
 Fasting plasma glucose (FPG) = 95 – 125 mg/dl
 1-hour post 75 g oral glucose load ≥ 180 mg/dl*
 2-hour post 75 g oral glucose load = 153 – 199 mg/dl
* There are no established criteria for the diagnosis of diabetes based on the 1-hour post glucose load value.
Screening of Gestational Diabetes Mellitus (GDM) – Current protocol in Gaza

Urine stick (glucose in urine)

(Booking Visit)
First ANC Visit

Negative Positive

Fasting Plasma Glucose

< 95 mg/dL 95 – 126 mg/dL ≥ 126 mg/dL

Diet & Exercise for 2 weeks

Fasting Plasma Glucose
Fasting Plasma Glucose
24th – 28th week

< 95 mg/dL 95 – 126 mg/dL ≥ 126 mg/dL ≥ 95 mg/dL

Diet & Exercise for 2 weeks

Fasting Plasma Glucose

< 95 mg/dL ≥ 95 mg/dL

Non-diabetic Likely Diabetes

No further action Refer to diabetic
clinic
Screening Interval

Patients with prediabetes: yearly.

Women who were diagnosed with GDM: lifelong testing at least

every 3 years.

If results are normal: a minimum of 3-year intervals, with

consideration of more frequent testing depending on initial results
and risk status.
Comprehensive Medical
Evaluation & Assessment
of Comorbidities
A patient-centered communication style that uses person-
centered and strength-based language and active listening; elicits
patient preferences and beliefs; and assesses literacy, numeracy,
and potential barriers to care should be used.

A successful medical evaluation depends on beneficial interactions

between the patient and the care team.

Individuals with diabetes must assume an active role in their care.

The goals of treatment for diabetes are to prevent or delay
complications and optimize quality of life.

The use of person-centered, strength based, empowering language

that is respectful and free of stigma in diabetes care and
education can help to inform and motivate people.

Use language that is person-centered (e.g., “person with

diabetes” is preferred over “diabetic”).
Comprehensive Medical Evaluation

A complete medical evaluation at the initial visit to confirm the

diagnosis and classify diabetes.

 Evaluate for complications and potential comorbid conditions.

 Review previous treatment and risk factor control in patients

with established diabetes.
Develop a plan for continuing care.

A follow-up visit should include most components of the initial

comprehensive medical evaluation.

Ongoing management should be guided by the assessment of

overall health status, diabetes complications, CV risk,
hypoglycemia risk.
Glycemic Goals

An A1C goal for many nonpregnant adults of <7% without significant
hypoglycemia is appropriate.

Achievement of lower A1C levels than the goal of 7% may be

acceptable and even beneficial if it can be achieved safely without
significant hypoglycemia or other adverse effects of treatment.

Less stringent A1C goals (such as <8% may be appropriate for patients
with limited life expectancy or where the harms of treatment are
greater than the benefits.
 Summary of Glycemic Recommendations for Many Nonpregnant
Adults With Diabetes (ADA 2022)
A1C <7.0%
Preprandial capillary 80–130 mg/dL
plasma glucose
Peak postprandial capillary <180 mg/dL
plasma glucose†

Goals should be individualized based on duration of diabetes, age/life expectancy,

comorbid conditions, known CVD or advanced microvascular complications,
hypoglycemia unawareness, and individual patient considerations.
†Postprandial glucose may be targeted if A1C goals are not met despite reaching
preprandial glucose goals. Postprandial glucose measurements should be made 1–2 hours
after the beginning of the meal, generally peak levels in patients with diabetes.
Facilitating Behavior Change and Well-
Being to Improve Outcomes
Goals: Achieving diabetes treatment goals and maximizing quality of life.

Essentials to achieving these goals are:-

Diabetes Self Management Education and Support (DSMES)

Medical nutrition therapy (MNT)
Routine physical activity
Smoking cessation counseling
Psychosocial care
Diabetes Self Management Education
and Support (DSMES)
There are four critical times to evaluate the need for DSMES to
promote skills acquisition in support of regimen implementation, MNT,
and well-being:

At diagnosis
Annually and/or when not meeting treatment targets
Complicating factors develop (medical, physical, psychosocial)
Transitions in life and care
Medical Nutrition Therapy (MNT)

Nutrition therapy plays an integral role in overall diabetes

management.

MNT delivered by a registered dietitian nutritionist is associated

with A1C absolute decreases of 1.0–1.9% for people with type 1
diabetes and 0.3–2.0% for people with type 2 diabetes.
Goals of Nutrition Therapy for Adults

To promote and support healthful eating patterns, emphasizing a

variety of nutrient-dense foods in appropriate portion sizes, to
improve overall health and:

Achieve and maintain body weight goals

Attain individualized glycemic, blood pressure, and lipid goals
Delay or prevent the complications of diabetes
To address individual nutrition needs based on personal and
cultural preferences, access to healthful foods, willingness and
ability to make behavioral changes

To maintain the pleasure of eating by providing nonjudgmental

messages about food choices while limiting food choices only when
indicated by scientific evidence

To provide a person with diabetes the practical tools for

developing healthy eating patterns rather than focusing on
individual macronutrients, micronutrients, or single foods
Weight Management

A variety of eating plans, varying in macronutrient composition,

can be used effectively and safely in the short term (1–2 years) to
achieve weight loss in people with diabetes.

Individualized meal plan containing: vegetables, fruits, legumes,

dairy, lean sources of protein (including plant-based sources as
well as lean meats, fish, and poultry), nuts, seeds, and whole
grains.
Physical Activity

Children and adolescents with type 1 or type 2 diabetes or

prediabetes:

60 minutes/day or more of moderate- or vigorous-intensity

aerobic activity at least 3 days/week with

vigorous muscle strengthening and bone-strengthening activities at

least 3 days/week.
Physical Activity

Most adults with type 1 and type 2 diabetes:

150 minutes or more of moderate- to vigorous-intensity aerobic activity per

week, spread over at least 3 days/week, with no more than 2 consecutive days
without activity.

Shorter durations (minimum 75 minutes/week) of vigorous-intensity or interval

training may be sufficient for younger and more physically fit individuals.

2–3 sessions/week of resistance exercise on nonconsecutive days.

Physical Activity

For all adults, and particularly those with type 2 diabetes prolonged
sitting should be interrupted every 30 minutes.

Flexibility training and balance training are recommended 2–3

times/week for older adults with diabetes.

Evaluate baseline physical activity and sedentary time. Promote

increase in nonsedentary activities above baseline for sedentary
individuals with type 1 and type 2 diabetes. Examples include walking,
housework, gardening, swimming.
Hypoglycemia

In individuals taking insulin and/or insulin secretagogues,

physical activity may cause hypoglycemia if the medication dose
or carbohydrate consumption is not adjusted for the exercise bout
and post-bout impact on glucose.

Educate to check blood glucose before and after exercise and

about the potential prolonged effects of exercise.
Exercise in the Presence of
Microvascular Complications
Proliferative diabetic retinopathy or severe nonproliferative retinopathy:
Risk of vitreous hemorrhage or retinal detachment in vigorous-intensity
aerobic or resistance exercise.

Peripheral neuropathy: Increased risk of skin infection and Charcot joint

destruction with some forms of exercise. They should wear proper footwear
and examine their feet daily.

Autonomic neuropathy: Risk of exercise-induced injury through decreased

cardiac responsiveness to exercise, postural hypotension, impaired
thermoregulation, and greater susceptibility to hypoglycemia.
Smoking Cessation

Advise all patients not to use cigarettes and other tobacco

products or e-cigarettes.

After identification of tobacco or e-cigarette use, include smoking

cessation counseling and other forms of treatment as a routine
component of diabetes care.
Psychosocial Issues

Screening and follow-up may include, attitudes about diabetes,

expectations for medical management and outcomes, affect or mood,
general and diabetes-related quality of life, available resources
(financial, social, and emotional), and psychiatric history.

Assess for symptoms of diabetes distress, depression, anxiety,

disordered eating, and cognition at the initial visit, at periodic
intervals, and when there is a change in disease, treatment, or life.

Include caregivers and family members in this assessment.

Foot Care

Perform a comprehensive foot evaluation at least annually to identify

risk factors for ulcers and amputations.

Patients with evidence of sensory loss or prior ulceration or

amputation should have their feet inspected at every visit.

Obtain a prior history of ulceration, amputation, Charcot foot,

angioplasty or vascular surgery, cigarette smoking, retinopathy, and
renal disease and assess current symptoms of neuropathy (pain, burning,
numbness) and vascular disease (leg fatigue, claudication).
The foot examination should include:-

Inspection of the skin

Assessment of foot deformities
Neurological assessment (10-g monofilament testing with at least
one other assessment: pinprick, temperature, vibration)
Vascular assessment (including pulses in the legs and feet).
Patients with symptoms of claudication or decreased or absent pedal
pulses should be referred for ankle-brachial index and for further
vascular assessment as appropriate.

A multidisciplinary approach is recommended for individuals with foot

ulcers and high-risk feet.

Refer patients who smoke or who have histories of prior lower-extremity

complications, loss of protective sensation, structural abnormalities, or
PAD to foot care specialists.
Provide general preventive foot self-care education to all patients with diabetes.

Specialized therapeutic footwear is recommended for high-risk patients:

Severe neuropathy
Foot deformities
Ulcers
Callous formation
Poor peripheral circulation
History of amputation
 Self-Management
Self-Management Collaborate with your patient to create an action plan
Diabetes Education Enable timely, culturally and literacy appropriate diabetes education
 The ADA acknowledges that there is no one-size-fits-all eating pattern for individuals with
Nutrition type 2 diabetes.
 Highlighting the importance of starting the patient his day with breakfast.
 Minimum 150 minutes aerobic activity per week and resistance exercise 2-3 times per
week
Physical Activity
 Reduce sedentary time = break up > 30 minutes spent sitting
 ≥ 60 min physical activity/day for children with diabetes or Prediabetes
Weight loss (5-10% of initial Can substantially improve glycemic control and cardiovascular disease risk factors in
weight) overweight patients
Counsel about adherence (dose, timing, frequency), anticipated effects, and mechanism of
Medication
action
Hypoglycemia Counsel about the prevention, recognition, and treatment of drug-induced hypoglycemia
Not on insulin: Individualized to type of antihyperglycemic agents, level of control, and risk
of hypoglycemia
Self-Monitoring Blood Glucose
(SMBG) On insulin only once a day: SMBG once a day at variable times

On insulin > once a day: SMBG 3 times per day including pre- and post-prandial values

Foot Care Educate on proper foot care including daily foot inspection

Common Mental Disorders Screen for common mental disorders using a standardized questionnaire (e.g., GHQ-12)

Smoking Cessation Include formal smoking prevention and cessation counseling

Pharmacologic Therapy for Adults With
Type 2 Diabetes
First-line therapy depends on comorbidities, patient centered
treatment factors and generally includes metformin.

(Glucagon-like peptide 1 [GLP-1] receptor agonists, sodium–glucose

cotransporter 2 [SGLT2] inhibitors), with or without metformin, are
appropriate initial therapy for individuals with or at high risk for ASCVD,
HF, and/or chronic kidney disease (CKD).

Metformin should be continued upon initiation of insulin (unless

contraindicated or not tolerated) for glycemic and metabolic benefits.
Early combination therapy can be considered in some patients at treatment
initiation to extend the time to treatment failure.

Medication regimen and medication-taking behavior should be reevaluated

at regular intervals (every 3–6 months) and adjusted as needed.

Glycemic status should be assessed, with treatment modified regularly

(e.g., at least twice yearly if stable and more often if not at goal).
Early introduction of insulin:

Ongoing catabolism (weight loss)

Symptoms of hyperglycemia
A1C levels (>10%)
Blood glucose levels (≥300 mg/dL)
Drug Classes

Biguanides
Sulfonylureas
Meglitinide derivatives
Alpha-glucosidase inhibitors
Thiazolidinediones (TZDs)
Glucagonlike peptide–1 (GLP-1) agonists
Dipeptidyl peptidase IV (DPP-4) inhibitors
Selective sodium-glucose transporter–2 (SGLT-2) inhibitors
Nonsteroidal mineralocorticoid receptor (MR) antagonists 
Insulins
Amylinomimetics
Bile acid sequestrants
Dopamine agonists
Biguanides (Metformin)

Metformin lowers basal and postprandial plasma glucose levels.

Metformin works by decreasing hepatic gluconeogenesis.

It also decreases intestinal absorption of glucose.

It also improves insulin sensitivity by increasing peripheral glucose

uptake and utilization.
Sulfonylureas (eg, glyburide, glipizide,
glimepiride, gliclazide, glibenclamide)
Insulin secretagogues that stimulate insulin release from
pancreatic beta cells and probably have the greatest efficacy for
glycemic lowering of any of the oral agents (However, that effect
is only short-term and quickly dissipates).

Sulfonylureas may also enhance peripheral sensitivity to insulin

secondary to an increase in insulin receptors or to changes in the
events following insulin-receptor binding.
Meglitinide derivatives (eg,
repaglinide, nateglinide)
Meglitinides are much shorter-acting insulin secretagogues than
the sulfonylureas are, with preprandial dosing potentially
achieving more physiologic insulin release and less risk for
hypoglycemia. 
Alpha-glucosidase inhibitors

These agents delay sugar absorption and help to prevent

postprandial glucose surges.

Alpha-glucosidase inhibitors prolong the absorption of

carbohydrates, but their induction of flatulence greatly limits
their use.

They should be titrated slowly to reduce gastrointestinal (GI)

intolerance.
Thiazolidinediones (eg, pioglitazone
[Actos], rosiglitazone [Avandia])
TZDs act as insulin sensitizers; thus, they require the presence of
insulin to work. They must be taken for 12-16 weeks to achieve
maximal effect.
Glucagonlike peptide–1 agonists (ie,
exenatide, liraglutide, albiglutide,
dulaglutide)
GLP-1 agonists mimic the endogenous incretin GLP-1; they
stimulate glucose-dependent insulin release, reduce glucagon, and
slow gastric emptying. The use of a GLP-1 in addition to metformin
and/or a sulfonylurea may result in modest weight loss.
Dipeptidyl peptidase IV inhibitors (eg,
sitagliptin, saxagliptin, linagliptin,
vildagliptin)
DPP-4 inhibitors are a class of drugs that prolong the action of
incretin hormones. DPP-4 degrades numerous biologically active
peptides, including the endogenous incretins GLP-1 and glucose-
dependent insulinotropic polypeptide (GIP).

They are given once daily and are weight neutral.

Selective sodium-glucose transporter-2
inhibitors (dapagliflozin, empagliflozin)
SGLT-2 inhibition lowers the renal glucose threshold (ie, the
plasma glucose concentration that exceeds the maximum glucose
reabsorption capacity of the kidney).

Lowering the renal glucose threshold results in increased urinary

glucose excretion.
 Drug-Specific and Patient Factors to Consider When Selecting Antihyperglycemic
Treatment in Adults With Type 2 Diabetes
CV effects Renal effects
Additional considerations
ASCD HF Progression of
Dosing/use considerations
DKD

Metformin Potential Neutral Neutral Contraindicated with - GIT Side effects common
Benefit eGFR <30 mL/min/1.73 (diarrhea, nausea)
m - Potential for B12
deficiency
SGLT2 Benefit: Benefit: Benefit: Glucose-lowering effect - Should be discontinued
inhibitors empagliflozin empagliflozin, canagliflozin, is lower for SGLT2 before any scheduled
canagliflozin canagliflozin, empagliflozin, inhibitors at lower eGFR surgery to avoid potential
dapagliflozin, dapagliflozin risk for DKA risk (all
ertugliflozin agents, rare in TZD)
- Risk of bone fractures
(canagliflozin)
- Genitourinary infections
- Risk of Fournier’s
gangrene
- Risk of volume depletion,
hypotension
- High LDL cholesterol
 CV effects Renal effects
Additional considerations

ASCD HF Progression of Dosing/use considerations

DKD
GLP-1 RAs Benefit: Neutral Benefit on renal See labels for renal dose FDA Black Box: Risk of
dulaglutide, end points in considerations of individual thyroid C-cell tumors in
liraglutide, CVOTs, driven agents rodents; human relevance
semaglutide by albuminuria No dose adjustment for not determined (liraglutide,
(SQ) outcomes: dulaglutide, liraglutide, dulaglutide, exenatide
Neutral: liraglutide, Semaglutide extended release,
exenatide semaglutide Caution when initiating or semaglutide)
once (SQ), increasing dose due to Gl side effects common
weekly, dulaglutide potential risk of nausea, (nausea, vomiting, diarrhea)
lixisenatide vomiting, diarrhea, or Injection site reactions
dehydration. Monitor renal Pancreatitis has been
function in patients reported in clinical
reporting severe adverse Gl trials but causality has not
reactions when initiating or been established.
increasing dose of therapy. Discontinue if pancreatitis
is suspected.
 CV effects Renal effects

Progression Dosing/use Additional considerations

ASCD HF
of DKD considerations

DPP-4 Neutral Potential Neutral Renal dose adjustment Pancreatitis has been reported in
inhibitors risk: required (sitagliptin, clinical trials but causality has not
saxagliptin saxagliptin, been established. Discontinue if
alogliptin); pancreatitis is suspected.
can be used in renal Joint pain
impairment
No dose adjustment
required for linagliptin
Thiazolidi Potential Increased Neutral No dose adjustment FDA Black Box: Congestive heart
nediones benefit: risk required failure (pioglitazone,
pioglitazone Generally not rosiglitazone)
recommended in renal Fluid retention (edema; heart
impairment due to failure)
potential for fluid Benefit in NASH
retention Risk of bone fractures
Bladder cancer (pioglitazone)
LDL cholesterol (rosiglitazone)
 CV effects Renal effects
Additional considerations
Progression Dosing/use
ASCD HF
of DKD considerations

Sulfonylureas Neutral Neutral Neutral Glyburide: generally FDA Special Warning on increased
(2nd generation) not recommended in risk of cardiovascular mortality
chronic kidney disease based on studies of an older
Glipizide and sulfonylurea (tolbutamide)
glimepiride:
initiate conservatively
to avoid hypoglycemia
Insuli Human Neutral Neutral Neutral Lower insulin doses Injection site reactions
n insulin required with a Higher risk of hypoglycemia with
Analogs decrease in eGFR; human insulin (NPH or premixed
titrate per clinical formulations) vs. analogs
response
 Weight Oral
Class Usual maintenance dose Efficacy Hypoglycemia Cost
change /SQ

Metformin 500-2000 mg per day High No Neutral Low Oral

(Biguanides) (potential for
modest loss)
SGLT2 inhibitors - Canagliflozin (Invokana) Intermediate No Loss High Oral
(sodium-glucose co- 100 – 300 mg daily
transporter-2)
inhibitors - Dapagliflozin (Forxiga)
5 – 10 mg daily

- Empagliflozin (Jardiance)
10 – 25 mg daily
 Weight
Class Usual maintenance dose Efficacy Hypoglycemia Cost Oral/SQ
change

GLP-1 RAs - Exenatide (Byetta) High No Loss High SQ; oral

(Glucagon-like 10 mcg twice daily (semaglutide)
peptide-1 Receptor - Liraglutide (Victoza)
Agonists) 1.2-1.8 mg once daily

DPP-4 inhibitors Sitagliptin, Vildagliptin Intermediate No Neutral Oral

(Gliptins) 50-100 mg once daily

Thiazolidinediones - Pioglitazone (Actos) High No Gain Low Oral

(TZD) 15-30 mg once daily
- Rosiglitazone (Avandia)
4-8mg daily as single or
as divided doses
 Weight
Class Usual maintenance dose Efficacy Hypoglycemia Cost Oral/SQ
change

Sulfonylureas - Gliclazide (diamicron) High Yes Gain Low Oral

(2nd generation) 80-320 mg per day (doses ˃
160 mg should be twice a
day)
- Glimepiride (Amaryl) 1-8 mg
once daily
- Glibenclamide (Daonil) 2.5-
20 mg twice daily
 Weight
Class Usual dose Efficacy Hypoglycemia Cost Oral/SQ
change

Insulin Human - Rapid-acting analogues High Yes Gain Low (SQ) SQ;
insulin (Aspart, Apidra) inhaled
Analogs - Short-acting (regular) High SQ
- Intermediate-acting (NPH)
- Long-acting basal analogues
Detemir (levemir), Glargine
(Lantus):
Start: 10 U/day or 0.1 – 0.2
U/Kg/day .
Adjust: 10 – 15% or 2 – 4 U once
or twice weekly to reach
target.
- Premixed (Regular + NPH)
Start: Divide dose into 2/3 at
morning and 1/3 at evening.
Adjust: ↑ dose by 1 – 2 U or 10 –
15% once or twice weekly.
Insulin Therapy
The progressive nature of T2DM should be regularly and
objectively explained. Avoid using insulin as a threat or
describing it as a sign of personal failure or punishment.

Educating and involving patients in insulin management is

beneficial.

Comprehensive education regarding self-monitoring of blood

glucose, diet, and the avoidance and appropriate treatment of
hypoglycemia are critically important.
Basal Insulin

Basal insulin alone is the most convenient initial insulin regimen

and can be added to metformin and other oral agents.

Starting doses can be estimated based on body weight (0.1–0.2

units/kg/day) and the degree of hyperglycemia, with
individualized titration over days to weeks as needed.

The principal action is to restrain hepatic glucose production and

limit hyperglycemia overnight and between meals.
Control of fasting glucose can be achieved with human NPH insulin or
a long-acting insulin analog.

Long acting basal analogs (U-100 glargine or detemir) have been

demonstrated to reduce the risk of symptomatic and nocturnal
hypoglycemia compared with NPH insulin.

Longer-acting basal analogs (U-300 glargine or degludec) may convey

a lower hypoglycemia risk compared with U-100 glargine when used in
combination with oral agents.
Prandial Insulin

Many individuals with type 2 diabetes require doses of insulin before meals,
in addition to basal insulin, to reach glycemic targets.

A dose of 4 units or 10% of the amount of basal insulin at the largest meal or
the meal with the greatest postprandial excursion is a safe estimate for
initiating therapy.

Individuals with type 2 diabetes require higher daily doses (~1 unit/kg) than
those with type 1 diabetes, and have lower rates of hypoglycemia. With
significant additions to the prandial insulin dose, particularly with the
evening meal, consideration should be given to decreasing basal insulin.
Concentrated Insulins

U-500 regular insulin is, by definition, five times more concentrated than U-
100 regular insulin.

U-500 regular insulin has distinct pharmacokinetics with delayed onset and
longer duration of action, has characteristics more like an
intermediateacting (NPH) insulin, and can be used as two or three daily
injections.

U-300 glargine and U-200 degludec are three and two times as concentrated
as their U-100 formulations, respectively, and allow higher doses of basal
insulin administration per volume used.
Inhaled Insulin

Inhaled insulin is available as a rapid-acting insulin.

Inhaled insulin is contraindicated in individuals with chronic lung

disease, such as asthma and COPD, and is not recommended in
individuals who smoke or who recently stopped smoking.

All individuals require spirometry (FEV1) testing to identify

potential lung disease prior to and after starting inhaled insulin.
Comorbidities of Diabetes
Hypertension / Blood Pressure Control

Hypertension (sustained blood pressure ≥140/90 mmHg), is common

among patients with either type 1 or type 2 diabetes.

BP should be measured at every routine clinical visit. When possible,

patients found to have elevated BP (≥ 140/ 90 mmHg) should have BP
confirmed using multiple readings to diagnose hypertension.

Patients with blood pressure ≥ 180/110 mmHg and CVD could be

diagnosed with hypertension at a single visit.
Hypertension / Treatment Goals

BP targets should be individualized through a shared decision-making process

that addresses CV risk, potential adverse effects of antihypertensive
medications, and patient preferences.

For individuals with diabetes and hypertension at higher CV risk, a BP

target of <130/80 mmHg may be appropriate, if it can be safely attained.

For individuals with diabetes and hypertension at lower risk for CVD, treat
to a blood pressure target of <140/90 mmHg.
Confirmed BP ≥140/90 mmHg should, in addition to lifestyle
therapy, have prompt initiation of pharmacologic therapy.

Confirmed BP ≥160/100 mmHg should, in addition to lifestyle

therapy, have prompt initiation and timely titration of two drugs
demonstrated to reduce CV events in patients with diabetes.

Treatment for hypertension should include drug classes

demonstrated to reduce CV events in patients with diabetes.
ACE inhibitors or ARBs: First-line therapy for hypertension in
people with diabetes and coronary artery disease (CAD).

An ACE inhibitor or ARB are recommended first-line treatment

for hypertension in patients with diabetes and CKD.

For patients treated with an ACE inhibitor, ARB, or diuretic,

serum creatinine/eGFR and serum potassium levels should be
monitored at least annually.
Lipid Management

Lifestyle modification should be recommended to improve the

lipid profile and reduce the risk of developing ASCVD.

Intensify lifestyle therapy and optimize glycemic control for

patients with elevated triglyceride levels (≥150 mg/dL and/ or low
HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women).
Ongoing Therapy and Monitoring With
Lipid Panel
In adults not taking statins: Obtain a lipid profile at the time of diabetes
diagnosis and every 5 years thereafter if under the age of 40 years, or more
frequently if indicated.

Obtain a lipid profile (to monitor the response to therapy and inform
medication adherence):

At initiation of statins or other lipid-lowering therapy

4–12 weeks after initiation or a change in dose
Annually thereafter
Statin Treatment for Primary
Prevention
Patients with diabetes 40–75 Y. without ASCVD: Moderate-
intensity statin therapy in addition to lifestyle therapy.
Patients with diabetes 20–39 Y. with additional ASCVD risk
factors: Statin therapy in addition to lifestyle therapy.
Patients with diabetes at with multiple ASCVD risk factors or
aged 50–70 Y.: Use high intensity statin therapy.
In adults with diabetes and 10-year ASCVD risk of 20% or
higher: Add ezetimibe to maximally tolerated statin therapy to
reduce LDL cholesterol levels by 50% or more.
Statin Treatment / Secondary
Prevention
Patients of all ages with diabetes and ASCVD: High-intensity statin therapy +
lifestyle therapy.

Patients with diabetes and ASCVD considered very high risk, if LDL cholesterol is
≥70 mg/dL on maximally tolerated statin dose: Add ezetimibe.

In adults with diabetes aged >75 years already on statin therapy: it is reasonable
to continue statin treatment.

In adults with diabetes aged >75 years: it may be reasonable to initiate statin
therapy after discussion of potential benefits and risks.
Antiplatelet Agents

Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those

with diabetes and a history of ASCVD.

If aspirin allergy, clopidogrel (75 mg/day) should be used.

Dual antiplatelet therapy (low-dose aspirin and a P2Y12 inhibitor) is reasonable for
a year after an acute coronary syndrome.

Long-term treatment with dual antiplatelet therapy should be considered with prior
coronary intervention, high ischemic risk, and low bleeding risk to prevent major
adverse CV events.
Combination therapy with aspirin plus low-dose rivaroxaban should
be considered for patients with stable CAD and/or PAD and low
bleeding risk to prevent major adverse limb and CV events.

Aspirin therapy (75–162 mg/day) may be considered as a

primary prevention strategy in those with diabetes who are at
increased CV risk.
Cardiovascular Disease / Screening

In asymptomatic patients, routine screening for CAD is not

recommended.

Consider investigations for CAD in the presence of:

Unexplained dyspnea, chest discomfort
Signs or symptoms of associated vascular disease (carotid bruits,
TIA, stroke, claudication, or PAD)
ECG abnormalities (e.g., Q waves)
Cardiovascular Disease / Treatment

Established ASCVD, multiple ASCVD risk factors, or diabetic kidney disease

(DKD): SGLT2 inhibitor with demonstrated CV.

Known ASCVD: ACE inhibitor or ARB.

Prior myocardial infarction: B-blockers for 3 years.

Heart failure: A b-blocker with proven CV outcomes.

Stable heart failure: Metformin may be continued if eGFR remains >30

mL/min/1.73 m2.
Special Groups
Older Adults

Over one-fourth of people >65 years of age have diabetes, and one-half of older
adults have prediabetes.

Consider the assessment of medical, psychological, functional, and social domains.

Screen for geriatric syndromes (i.e., polypharmacy, cognitive impairment,

depression, urinary incontinence, falls, and persistent pain and frailty).

Screening for diabetes complications in older adults should be individualized and

periodically revisited.
Older Adults / Hypoglycemia

Episodes of hypoglycemia should be ascertained and addressed at routine

visits due to greater risk of hypoglycemia.

For older adults with type 1 diabetes, CGM should be considered.

Higher risk of hypoglycemia for many reasons (insulin deficiency necessitating

insulin therapy and progressive renal insufficiency).

Patients and their caregivers should be routinely queried about hypoglycemia

and hypoglycemia unawareness.
Older Adults / Lifestyle Management

Optimal nutrition and protein intake is recommended; regular

exercise, including aerobic activity, weight-bearing exercise,
and/or resistance training, should be encouraged in all older
adults who can safely engage in such activities.

For older adults with type 2 diabetes, overweight/ obesity, and

capacity to safely exercise, an intensive lifestyle intervention
focused on dietary changes, physical activity, and modest weight
loss (e.g., 5–7%) should be considered.
Older Adults / Pharmacologic Therapy

Medication classes with low risk of hypoglycemia are preferred.

Overtreatment of diabetes is common in older adults and should be

avoided.

Metformin is the first-line agent for older adults with type 2 diabetes.

Simplification of the insulin regimen to match an individual's self-

management abilities to reduce hypoglycemia and disease related
distress without worsening glycemic control.
Children & Adolescents

Type 1 diabetes is the most common form of diabetes in youth. A

multidisciplinary team of specialists trained in pediatric diabetes
management should provide care for this population.

Type 2 diabetes in youth has increased over the past 20 years (5,000 new
cases per year in the United States).

 Type 2 diabetes in youth is different not only from type 1 diabetes, but also
from type 2 diabetes in adults, with a more rapid, progressive decline in b-
cell function and accelerated development of diabetes complications.
Children & Adolescents / Management

Treatment of youth-onset type 2 diabetes should include lifestyle

management, diabetes self-management education, and
pharmacologic treatment.

Current pharmacologic treatment options for youth-onset type 2

diabetes are limited to three classes of drugs: insulin,
metformin, and, in those ≥10 years of age with no
contraindications, GLP-1 RA indicated for use in youth.
Children & Adolescents / Glycemic
Targets
A reasonable A1C target for most children and adolescents with
type 2 diabetes is <7%.

More stringent A1C targets (such as <6.5% may be appropriate

for selected individual patients if they can be achieved without
significant hypoglycemia or other adverse effects of treatment.

Less stringent A1C goals (such as 7.5%) may be appropriate if

there is increased risk of hypoglycemia.
Pharmacologic Therapy for Adults with
Type 1 Diabetes
Most individuals with type 1 diabetes should be treated with multiple
daily injections of prandial and basal insulin, or continuous
subcutaneous insulin infusion.

Most individuals with type 1 diabetes should use rapid-acting insulin

analogs to reduce hypoglycemia risk.

Individuals with type 1 diabetes should receive education on how to

match mealtime insulin doses to carbohydrate intake, fat and protein
content, and anticipated physical activity.
Management of Diabetes in Pregnancy

Increasing prevalence in parallel with the worldwide epidemic of

obesity.

Specific risks of diabetes in pregnancy: spontaneous abortion, fetal

anomalies, preeclampsia, fetal demise, macrosomia, neonatal
hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress
syndrome, among others.

Diabetes in pregnancy may increase the risk of obesity, hypertension,

and type 2 diabetes in offspring later in life.
Preconception Counseling

Starting at puberty and continuing in all women with diabetes and

reproductive potential, preconception counseling should be
incorporated into routine diabetes care.

Family planning should be discussed, and effective contraception should

be prescribed and used until a woman's treatment regimen and A1C are
optimized for pregnancy.

Preconception counseling should address the importance of achieving

glucose levels as close to normal as is safely possible, ideally A1C <6.5%.
Preconception Care

Women with preexisting diabetes who are planning a pregnancy should

ideally be managed beginning in preconception in a multidisciplinary clinic
when available.

Women with preexisting type 1 or type 2 diabetes who are planning pregnancy
or who have become pregnant should be counseled on the risk of development
and/or progression of diabetic retinopathy.

Dilated eye examinations should occur ideally before pregnancy or in the

first trimester, and then patients should be monitored every trimester and
for 1 year postpartum.
Management of GDM
Lifestyle behavior change may suffice for the treatment of many women.

Insulin is the preferred medication for treating hyperglycemia in GDM.

Metformin and glyburide should not be used as first-line agents, as both
cross the placenta to the fetus.

Other oral and noninsulin injectable glucose-lowering medications lack long-

term safety data.

Metformin, when used to treat polycystic ovary syndrome and induce

ovulation, should be discontinued by the end of the first trimester.
Pregnancy and Drug Considerations

In pregnant patients with diabetes and chronic hypertension, a

blood pressure target of 110–135/85 mmHg is suggested.

(ACE inhibitors, ARBs, statins) should be stopped at conception

and avoided in sexually active women of childbearing age who
are not using reliable contraception.
Postpartum Care

Insulin requirements need to be evaluated and adjusted, as they are often roughly half the
prepregnancy requirements for the initial few days postpartum.

Screen women with a recent history of GDM at 4–12 weeks postpartum using the 75-g OGTT
and clinically appropriate nonpregnancy diagnostic criteria.

Women with a history of GDM found to have prediabetes should receive intensive lifestyle
interventions and/or metformin to prevent diabetes.

Women with a history of GDM should have lifelong screening for the development of type 2
diabetes or prediabetes every 1–3 years.
Complications of
Diabetes
Cardiovascular Disease (CVD)

Atherosclerotic cardiovascular disease (ASCVD)—presumed to be of

atherosclerotic origin—is the leading cause of morbidity and
mortality in diabetes.

Coronary artery disease (CAD)

Cerebrovascular disease
Peripheral artery disease (PAD)
HF
Cardiovascular Disease / Risk Factors

Duration of diabetes
Obesity/ overweight
Hypertension
Dyslipidemia
Smoking
A family history of premature coronary disease
CKD, and the presence of albuminuria

Risk factors should be assessed at least annually in all patients with diabetes to
prevent and manage both ASCVD and HF.
 Recommendations for vascular protection
For all patients with diabetes:

The ABCDEs

A A1C – optimal glycemic control (usually ≤ 7 %)

B BP – optimal blood pressure control (< 130/80

mmHg)

C Cholesterol – LDL-C ≤ 70 mg/dl if decision made

to treat

D Drugs – to protect the heart (see algorithm)

A – ACEi or ARB
S – Statin
A – ASA

E Exercise – regular physical activity, healthy diet,

achievement and maintenance of healthy body weight

S Smoking cessation

* Dose adjustments or additional lipid therapy warranted if lipid target (LDL-C ≤70 mg/dl) not being met.
# ACE-inhibitor or ARB should be given at doses that have demonstrated vascular protection.
Chronic Kidney Disease (CKD)

CKD is diagnosed by the persistent elevation of urinary albumin excretion

(albuminuria), low eGFR, or other manifestations of kidney damage.

CKD attributable to diabetes (DKD) typically develops after diabetes duration

of 10 years in type 1 but may be present at diagnosis of type 2 diabetes.

CKD can progress to ESRD requiring dialysis or kidney transplantation and is

the leading cause of ESRD.

CKD also markedly increases CV risk.

Chronic Kidney Disease / Screening

At least annually, urinary albumin (e.g., spot UACR) and eGFR
should be assessed in patients with type 1 diabetes with
duration of ≥5 years and in all patients with type 2 diabetes
regardless of treatment.

Patients with diabetes and urinary albumin ≥300 mg/g

creatinine and/or an eGFR 30–60mL/min/1.73 m2 should be
monitored twice annually to guide therapy.
Chronic Kidney Disease / Treatment
Optimize glucose control.

For patients with type 2 diabetes and DKD: SGLT2 inhibitor in patients
with an eGFR ≥25 mL/min/1.73 m2 and urinary albumin ≥300 mg.

In patients with type 2 diabetes and CKD: SGLT2 inhibitors

additionally for CV risk reduction when eGFR and urinary albumin
creatinine are ≥25 mL/min/1.73 m2 or ≥300 mg/g, respectively.

Optimization of blood pressure control to reduce the risk or slow the

progression of CKD.
Do not discontinue renin-angiotensin system blockade for minor
increases in serum creatinine (≤30%) in the absence of volume
depletion.

For people with stage 3 or higher CKD, dietary protein intake

should be a maximum of 0.8 g/kg body weight per day.

An ACE inhibitor or an ARB is not recommended for the primary

prevention of CKD in patients with diabetes who have normal
blood pressure, normal UACR (<30 mg/g creatinine), and normal
eGFR.
Diagnosis and Staging of Diabetic
Kidney Disease (DKD)
Staging is based on the presence and degree of albuminuria and/or
reduced eGFR in the absence of signs or symptoms of other primary
causes of kidney damage.

Two of three specimens of UACR collected within a 3- to 6-month

period should be abnormal before considering a patient to have
albuminuria.

eGFR should be calculated from serum creatinine using a validated

formula.
Chronic Kidney Disease / Interventions

Metformin may be considered as the initial glucose-lowering medication in

the setting of CKD.

It is contraindicated in patients with an eGFR<30 mL/min/1.73 m2; the

benefits and risks of continuing treatment should be reassessed when eGFR
falls to <45 mL/min/1.73 m2; metformin should not be initiated for patients
with an eGFR <45 mL/ min/1.73 m2;

Metformin should be temporarily discontinued at the time of or before

iodinated contrast imaging procedures in patients with eGFR 30–60
mL/min/1.73 m2.
SGLT2 inhibitors should be given to all patients with stage 3 CKD or higher and
type 2 diabetes regardless of glycemic control, as they slow CKD progression
and reduce HF risk independent of glycemic control.

Empagliflozin and dapagliflozin are approved by the FDA for use with eGFR 25–
45 mL/min/1.73 m2 for kidney/HF outcomes. Empagliflozin can be started with
eGFR >30 mL/min/1.73 m2 (though pivotal trials for each included participants
with eGFR $30 mL/min/1.73 m2 and demonstrated benefit in subgroups with
low eGFR).

Canagliflozin is approved to be initiated to eGFR levels of 30 mL/min/1.73 m2.

 Nephropathy
Recommendations:
 Optimize glucose control to reduce the risk or slow the progression of diabetic kidney disease (DKD).
 Optimize blood pressure control to reduce the risk or slow the progression of diabetic kidney disease.

Stages of Diabetic Nephropathy by Level of Urinary Albumin Level

Urine ACR (mg/mmol) 24 hours urine collection for
Stages of Nephropathy Urine dipstick for protein
(Albumin-to-Creatinine Ratio) Albumin

Normal Negative <2 < 30 mg/day

Microalbuminuria Negative 2 – 20 30 – 300 mg/day
Overt Nephropathy Positive ˃ 20 ˃ 300 mg/day
˃ 67 ˃ 1000 mg/day

Potential Causes for Transient Albuminuria

 Recent major exercise
 Urinary Tract Infection
 Febrile illness
 Decompensated congestive heart failure
 Menstruation
 Acute severe elevation in blood glucose
 Acute severe elevation in blood pressure
 For people with diabetic kidney disease, reducing the amount of dietary protein below the recommended daily allowance of 0.8
g/kg/day (based on ideal body weight) is not recommended because it does not alter glycemic measures, cardiovascular risk
measures, or the course of GFR decline.
 Retinopathy
Optimize glycemic control, BP, and serum lipid to reduce the risk or slow the progression of diabetic
retinopathy.
Screening Initial dilated and comprehensive eye exam by an ophthalmologist or optometrist:
 Adults with type 1 diabetes: Within 5 years after diagnosis
 Patients with type 2 diabetes: Upon diagnosis
 If no retinopathy for ≥1 eye exam: Consider exams every 1-2 years
 If retinopathy: Annual exam
 Retinopathy progressing or sight threatening: More frequent exams
Fundus photographs should be considered a screening tool, not a substitute for comprehensive
exam
Pregnant women or women planning pregnancy with preexisting diabetes
 Retinopathy counseling, eye exam in first trimester
 Close follow-up throughout pregnancy and 1 year postpartum

Treatment

Macular edema, severe NPDR (non-proliferative diabetic

Refer to ophthalmologist specializing in retinopathy
retinopathy), any PDR (proliferative diabetic retinopathy)

Indicated to reduce risk of vision loss for high-risk PDR,

Laser photocoagulation therapy clinically significant macular edema, some cases of severe
NPDR

Anti-VEGF (vascular endothelia growth factor) therapy Indicated for diabetic macular edema

The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection, as aspirin does
not increase the risk of retinal hemorrhage.
 Neuropathy
Screening Screen all patients for diabetic peripheral neuropathy
 Type 2 diabetes: At diagnosis and at least annually thereafter
 Type 1 diabetes: 5 years after diagnosis and at least annually thereafter
 Consider assessing for signs/symptoms of autonomic neuropathy with
microvascular complications

 Assessment for distal symmetric polyneuropathy should include a careful

history and assessment of either temperature or pinprick sensation (small-
fiber function) and vibration sensation using a 128-Hz tuning fork (for
large-fiber function).
 All patients should have annual 10-g monofilament testing to identify feet
at risk for ulceration and amputation.
Treatment
 Optimize glucose control to prevent or delay the development of neuropathy in
patients with type 1 diabetes and to slow the progression of neuropathy in patients
with type 2 diabetes.
 Pregabalin, duloxetine, or gabapentin are recommended as initial pharmacologic
treatments for neuropathic pain in diabetes.
Diabetic Emergencies
Hypoglycemia

Occurrence and risk for hypoglycemia should be reviewed at every encounter and
investigated as indicated.

Glucose (approximately 15–20 g) is the preferred treatment for the conscious individual
with blood glucose <70 mg/dL, although any form of carbohydrate that contains glucose
may be used.

Fifteen minutes after treatment, if BGM shows continued hypoglycemia, the treatment
should be repeated.

Once the BGM or glucose pattern is trending up, the individual should consume a meal or
snack to prevent recurrence of hypoglycemia.
Glucagon should be prescribed for all individuals at increased
risk of level 2 or 3 hypoglycemia. Caregivers, school personnel,
or family members providing support to these individuals should
know where it is and when and how to administer it.

Hypoglycemia unawareness or one or more episodes of level

hypoglycemia should trigger hypoglycemia avoidance education
and reevaluation and adjustment of the treatment regimen to
decrease hypoglycemia.
Insulin-treated patients with hypoglycemia unawareness, one
level 3 hypoglycemic event, or a pattern of unexplained level 2
hypoglycemia should be advised to raise their glycemic targets to
strictly avoid hypoglycemia for at least several weeks.

Ongoing assessment of cognitive function is suggested with

increased vigilance for hypoglycemia by the clinician, patient, and
caregivers if impaired or declining cognition is found.
 Classification of Hypoglycemia
Glycemic Criteria/Description
Level 1 Glucose <70 mg/dL and ≥54 mg/dL
Level 2 Glucose <54 mg/dL
Level 3 A severe event characterized by altered
mental and/or physical status requiring
assistance for treatment of
hypoglycemia
 Hypoglycemia
Hypoglycemia in diabetic patients is an abnormal low concentration of glucose in
the blood caused by insufficient food intake, excessive exercise, or over-dosage
with oral antihyperglycemic agents or insulin.

Symptoms of hypoglycemia Severity of hypoglycemia

Neurogenic
Neuroglycopenic Mild: Autonomic symptoms are present. The
(autonomic)
individual is able to self-treat.
Difficulty concentrating
Trembling
Confusion Moderate: Autonomic and neuroglycopenic
Palpitations
Weakness symptoms are present. The individual is able to self-
Sweating
Drowsiness treat.
Anxiety
Vision changes
Hunger Severe: Individual requires assistance of another
Difficulty speaking
Nausea person. Unconsciousness may occur. PG is typically
Headache
Tingling < 50 mg/dl
Dizziness

Examples of 15 g carbohydrate for treatment of mild to moderate hypoglycemia

 15 g glucose in the form of glucose tablets
 15 mL (3 teaspoons) or 3 packets of table sugar dissolved in water
 175 mL (3/4 cup) of juice or regular soft drink
 6 LifeSavers (1 = 2.5 g carbohydrate)
 15 mL (1 tablespoon) of honey

Note: In case of coma whatever the cause, treatment should be infusion of 5 – 10 % Dextrose immediately.
 Diabetic Ketoacidosis (DKA)
DKA results from lack of insulin especially with acute infections that increases
insulin demands. Occurs almost only in persons with type 1 diabetes, occasionally
in type 2 diabetes; it is a medical emergency that needs urgent hospitalization
and accounts for approximately 5 % mortality.
Causes

In order of frequency:
1. Omission or reduction of insulin
2. Undiagnosed diabetes Treatment of DKA
3. Intercurrent illness, especially acute infections

Signs and Symptoms  Rehydration (fluid replacement)

 Insulin administration
Symptoms develop over 
Characteristic features Bicarbonate therapy
several hours
 Potassium replacement for maintaining serum
 Polydipsia, polyuria Potassium
 Abdominal pain
 Smell of acetone on
(without localizing
breathing
signs)
 Kussmaul breathing
 Vomiting
(hyperventilation)
 Dehydration
 Warm, dry skin
 Drowsiness → Coma
→ Death

Note: In case of coma whatever the cause, treatment should be infusion of 5 – 10 % Dextrose immediately.
 Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNS)
HHNS, is a serious condition most frequently seen in older persons. HHNS occurs
more often in people with type 2. HHNS is usually brought on by something else,
such as an illness or infection
Symptoms of HHNS HHNS Clinical features
• Blood sugar level over 600 mg/dl
• Dry mouth Extreme thirst Diabetic hyperosmolar syndrome can lead to:
• Increase urination • Seizures
• Warm, dry skin that does not sweat • Heart attack
• High fever • Stroke
• Sleepiness or confusion • Coma
• Loss of vision
• Hallucinations (seeing or hearing things that are
not there) Emergency treatment can correct diabetic
• Weakness on one side of the body hyperosmolar syndrome within hours.
• Coma

Treatment of HHNS

Treatment typically includes:

 Intravenous fluids to counter dehydration
 Intravenous insulin to lower blood sugar levels
 Intravenous potassium, and occasionally sodium phosphate replacement to help cells function correctly
 Differential Diagnosis of Diabetic Ketoacidosis (DKA) &
Hyperglycemic Hyperosmolar State (HHS)
Parameter Normal range DKA HHS
Plasma glucose, mg/dL 76-115 ≥250 ≥600
Arterial pH* 7.35-7.45 ≤7.30 >7.30
Serum bicarbonate, mmol/L 22-28 ≤15 >15
Effective serum osmolality, mmol/kg 275-295 ≤320 >320
Anion gap,† mmol/L <12 >12 Variable
Serum ketones Negative Moderate to high None or trace
Urine ketones Negative Moderate to high None or trace
* If venous pH is used, a correction of 0.03 must be made.
†
Calculation: Na+ - (Cl- + HCO3-).

Diabetic Ketoacidosis (DKA) Hyperglycemic Hyperosmolar State (HHS)

Absolute (or near-absolute) insulin deficiency, Severe relative insulin deficiency, resulting in
resulting in • Profound hyperglycemia and hyperosmolality
• Severe hyperglycemia (from urinary free water losses)
• Ketone body production • No significant ketone production or acidosis
• Systemic acidosis
Develops over hours to 1-2 days Develops over days to weeks
Most common in type 1 diabetes, but increasingly Typically presents in type 2 or previously
seen in type 2 diabetes unrecognized diabetes
Higher mortality rate
 WHO CV Risk Charts
(10-year Risk of Fatal or
Non-Fatal CV Event)
 CVD Risk Charts (2019)
Charts Variables

 Age
 Sex
 Smoking
Laboratory-based charts
 Systolic Blood Pressure
 Presence or absence of Diabetes
 Total Cholesterol

 Age
 Sex
Non-laboratory-based charts  Smoking
 Systolic Blood Pressure
 Body Mass Index (BMI)
 Risk Levels and Colour Code
Colour Risk Follow-up
  Green <5%  Follow-up every 12 months
  Yellow 5% to <10%  Follow-up every 9 months
  Orange 10% to <20%  Follow-up every 6 months

 Follow-up every 3 months.

 If there is no reduction in cardiovascular risk after 6
months of follow-up, refer.
 All patients with established:
  Red 20% to <30%  CVD*
 DM + CVD*
 DM + CKD†
should be considered as having risk ≥20%.
 Follow-up every 3 months.
  Deep Red ≥30%  If there is no reduction in cardiovascular risk after 3
months of follow-up, refer.
*
CVD (cardiovascular disease): coronary heart disease, myocardial infarction, heart failure, transient ischemic attack,
cerebrovascular disease or peripheral vascular disease.
†
CKD (chronic kidney disease) is diagnosed by the persistent presence of elevated urinary albumin excretion (albuminuria), low
eGFR, or other manifestations of kidney damage. Among people with type 1 or type 2 diabetes, the presence of CKD markedly
increases CV risk and health care costs.
 Laboratory-Based Chart
(People without Diabetes)
Laboratory-Based Chart
(People with Diabetes)
Non-Laboratory-Based Risk Chart
Referral Criteria
Referral
Referral Reason
Code
1 High Cardiovascular Risk ≥ 20% if no improvement after follow-
up )according to CVR charts).
2 .Total cholesterol ≥271 mg/dl despite intensive antilipid therapy
3 SBP ˃180mmHg and/or DBP ˃120 mmHg with symptoms or signs of
Target Organ Damage*(Emergent referral).
4 BP ≥ 140/90 mmHg while on treatment with 3 antihypertensive
drugs.
5 BP ≥ 140 or ≥ 90 mmHg in people ˂ 30 years (to exclude secondary
.HTN)
6 :Fundoscopy
T2DM upon diagnosis and annually if normal.
T1DM 5 years after diagnosis and annually if normal.
HTN upon diagnosis and annually if normal.
7 :Diabetic foot ulcer
Non healing foot ulcer.
Presenting ulcer with previous vascular intervention.
Presenting ulcer with previous amputation.
 Referral
Referral Reason
Code
8 Newly diagnosed DM with urine ketones 2+ or in lean persons ˂ 30
years.
9 .≠Persistent albuminuria
10 DM with poor control despite maximal antihyperglycemic therapy.
11 Patients with symptoms of claudication or decreased or absent
pedal pulses should be referred for ankle-brachial index.
12 New chest pain, any symptoms or signs of HF, change of severity of
.angina, or symptoms of transient ischemic attack or stroke
13 .*Symptoms or signs of Target Organ Damage
14 Persistent or severely uncontrolled bronchial asthma or frequent
.exacerbations
15 .Other reasons (Specify)

*Symptoms & signs of Target Organ Damage (TOD): Chest pain, dyspnea, back pain, seizures, visual disturbances
and altered level of consciousness.

≠ Persistent albuminuria: defined as two of three positive samples over 6 months.

References

• ADA 2022
• Medscape 2022
• ADA 2021
• WHO 2021
• WHO PEN protocol 2020