DISCUSSION

DIABETES MELLITUS
HYPERGLYCEMIA

Increased Glucose
Production

Decreased Insulin
Secretion

Decreased Glucose
Utilization
Classification

Type 1 DM autoimmune ß-cell destruction → insulin deficiency

progressive loss of ß-cell insulin secretion frequently

Type 2 DM on the background of insulin resistance
 Specific Monogenic syndromes (neonatal diabetes, MODY)
types of Diseases of the exocrine pancreas (CF, pancreatitis)
Drug or chemical-induced diabetes (glucocorticoids)
diabetes

diabetes diagnosed in the second or third trimester of

Gestational pregnancy that was not clearly overt diabetes prior to
DM gestation
 Criteria for the Diagnosis of Diabetes

FPG ≥ 126 mg/dl (7.0 mmol/L)

- OR -

75g OGTT
2-hour PG ≥ 200 mg/dl (11.0 mmol/L)
- OR -

HbA1c ≥ 6.5 % (48mmol/mol)

- OR -

Random plasma glucose ≥ 200 mg/dl

with classic symptoms of hyperglycemia or
hyperglycemic crisis
 Criteria for the Diagnosis of Diabetes

FPG ≥ 126 mg/dl (7.0 mmol/L)

- OR -

75g OGTT
2-hour PG ≥ 200 mg/dl (11.0 mmol/L)
- OR -

HbA1c ≥ 6.5 % (48mmol/mol)

- OR -

Random plasma glucose ≥ 200 mg/dl

with classic symptoms of hyperglycemia or
hyperglycemic crisis
Criteria for the Diagnosis of Prediabetes

FPG 100 mg/dl to 125 mg/dl

(5.6 mmol/L to 6.9 mmol/L)
(Impaired Fasting Glucose)
- OR -

75g OGTT
2-hour PG 140 mg/dl to 199 mg/dl
(7.8 mmol/L to11.0 mmol/L)
(Impaired Glucose Tolerance)
- OR -

HbA1c 5.7 % to 6.4 % (39 - 47 mmol/mol)

 Criteria for the Diagnosis of Gestational Diabetes Mellitus
ONE-STEP STRATEGY
75-g Oral Glucose Tolerance Test at 24 – 28 weeks gestation in women not
previously diagnosed with diabetes.

Any of the following are met or exceeded:

FPG 92 mg/dl (5.1 mmol/L)
1-hour PG: 180 mg/dl (10.0 mmol/L)
2-hour PG 153mg/dl (8.5 mmol/L)
 Criteria for the Diagnosis of Gestational Diabetes Mellitus

TWO-STEP STRATEGY
Step 1: 50-g Glucose Load Test (nonfasting) at 24 – 28 weeks gestation in
women not previously diagnosed with diabetes.
If plasma glucose after 1 hour is ≥ 130 mg/dl (7.2 mmol/L), proceed to step 2.

Step 2: 100-g OGTT

At least 2 of the following are or exceeded
FPG 95 mg/dl (5.3 mmol/L)
1-hour PG 180 mg/dl (10.0 mmol/L)
2-hour PG 155 mg/dl (8.6 mmol/L)
3-hour PG 140 mg/dl (7.8 mmol/L)
 Criteria for testing for diabetes or prediabetes in asymptomatic adults
1. Testing should be considered in adults with overweight or obesity (BMI ≥ 25 kg/m 2 or 23 kg/m2 in
Asian Americans) who have one or more of the following risk factors:
 First-degree relative with diabetes
 High-risk race/ethnicity (e.g. African American, Latino, Native American, Asian American,
Pacific Islander)
 History of CVD
 Hypertension (≥ 140/90 mmHg or on therapy for hypertension)
 HDL < 35 mg/dl (0.90 mmol/L) and/or triglyceride > 250 mg/dl (2.82 mmol/L)
 Women with polycystic ovary syndrome
 Physical inactivity
 Other clinical conditions associated with insulin resistance (e.g. severe obesity, acanthosis
nigricans)

2. Patients with prediabetes (A1C ≥ 5.7 % [39 mmol/mol], IGT or IFG) should be tested yearly.
3. Women who were diagnosed with GDM should have a lifelong testing at least every 3 years.
4. For all other patients, testing should begin at age 45 years.
5. If results are normal, testing should be repeated at a minimum of 3-year intervals, with
consideration of more frequent testing depending on initial results and risk status.
6. HIV
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
Comprehensive Medical Evaluation and Assessment of Comorbidities

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Standards of Medical Care in Diabetes - 2021. Diabetes Care 2021;44(Suppl. 1):S40-S52
GOALS OF THERAPY

Eliminate symptoms related to hyperglycemia

Reduce/eliminate the long-term microvascular and

macrovascular complications of DM

Allow the patient to achieve as normal a lifestyle as

possible
Glycemic Targets for
Non-pregnant Adults with Diabetes
< 7.0 %
HBA1c
(53 mmol/mol)

80 – 130 mg/dl Preprandial capillary plasma

(4.4 – 7.2 mmol/L) glucose

< 180 mg/dl Peak postprandial capillary

(10.0 mmol/L) plasma glucose

TIR > 70% with time

AGP/GMI
below range < 4 %
 Mechanism of Action Examples HBA1c Agent-specific Contraindications
reduction (%) disadvantages
ORAL
Biguanides ↓ hepatic glucose production Metformin 1–2 Diarrhea, nausea, Renal insufficiency
lactic acidosis, (<45 ml/min GFR),
vitamin B12 CHF, radiographic
deficiency contrast studies,
acidosis

α-glucosidase ↓ GI glucose absorption Acarbose 0.5 – 0.8 GI flatulence Renal/liver disease

inhibitor Miglitol
Voglibose
Dipeptidyl Prolong endogenous GLP-1 Alogliptin 0.5 – 0.8 Angioedema/ Reduced dose with
peptidase IV action; Linagliptin urticarial and renal disease
inhibitors ↑ insulin, ↓ glucagon Saxaliptin immune-mediated
Sitagliptin dermatologic
Vildagliptin effects

Insulin ↑ insulin secretion Glibornuride 1–2 Hypoglycemia, Renal/liver disease

secretagogues: Gliclazide weight gain
Sulfonylureas Glimepiride
Gliplizide
Gliquidone
Glyburide
Glyclopyramide
 Mechanism of Action Examples HBA1c Agent-specific Contraindications
reduction (%) disadvantages
ORAL
Biguanides ↓ hepatic glucose production Metformin 1–2 Diarrhea, nausea, Renal insufficiency
lactic acidosis, (<45 ml/min GFR),
vitamin B12 CHF, radiographic
deficiency contrast studies,
acidosis

α-glucosidase ↓ GI glucose absorption Acarbose 0.5 – 0.8 GI flatulence Renal/liver disease

inhibitor Miglitol
Voglibose
Dipeptidyl Prolong endogenous GLP-1 Alogliptin 0.5 – 0.8 Angioedema/ Reduced dose with
peptidase IV action; Linagliptin urticarial and renal disease
inhibitors ↑ insulin, ↓ glucagon Saxaliptin immune-mediated
Sitagliptin dermatologic
Vildagliptin effects

Insulin ↑ insulin secretion Glibornuride 1–2 Hypoglycemia, Renal/liver disease

secretagogues: Gliclazide weight gain
Sulfonylureas Glimepiride
Gliplizide
Gliquidone
Glyburide
Glyclopyramide
 Mechanism of Action Examples HBA1c Agent-specific Contraindications
reduction (%) disadvantages

ORAL
Insulin ↑ insulin Mitiglinide 0.5 – 1.0 Hypoglycemia Renal/liver disease
secretagogues: Nateglinide
Non-sulfonylureas Repaglinide
Sodium-glucose ↑ renal glucose excretion Canagliflozin 0.5 – 1.0 Urinary and genital Moderate renal
cotransporter 2 Dapagliflozin infections, polyuria, insufficiency, insulin
inhibitors Empagliflozin dehydration, deficient DM
Ertugliflozin exacerbate
tendency to
hyperkalemia and
DKA

Thiazolidinediones ↓ insulin resistance; ↑ Pioglitazone 0.5 – 1.4 Peripheral edema, CHF, liver disease
glucose utilization Rosiglitazone CHF, weight gain,
fractures, macular
edema
 Mechanism of Action Examples HBA1c Agent-specific Contraindications
reduction (%) disadvantages

PARENTERAL
Amylin Agonists Slow gastric emptying time, Pramlintide 0.25 – 0.5 Injection, nausea, ↑ Agents that also
↓ glucagon risk of slow GI motility
hypoglycemia with
insulin

GLP-1 receptor ↑ insulin, ↓ glucagon, slow Albiglutide 0.5 - 1 Injection, nausea, ↑ Renal disease,
agonists gastric emptying, satiety Dulaglutide risk of agents that also
Exenatide hypoglycemia with slow GI motility;
Liraglutide insulin medullary
Lixisenatide secretagogues carcinoma of
Semaglutide thyroid, pancreatic
disease

Insulin ↑ glucose utilization; Injection, weight

↓ hepatic glucose gain, hypoglycemia
production, and other
anabolic actions

MEDICAL ↓ insulin resistance, ↑ insulin Low-calorie, low 1–3 Compliance

NUTRITION secretion fat diet, exercise difficult,
THERAPY Long term success
low
Early Initiation of Insulin
Evidence of on-going catabolism
(Weight loss)
HBA1c ≥ 10 %

FPG ≥ 300 mg/dL

Symptoms of hyperglycemia are
present
Suspect Diabetes Mellitus Type 1
Pharmacologic Approaches to Glycemic Treatment

Intensifying to injectable therapies (1 of 2)

Pharmacologic Approaches to
Glycemic Management:
Standards of Medical Care in
Diabetes - 2021. Diabetes Care
2021;44(Suppl. 1):S111-S124
Pharmacologic Approaches to Glycemic Treatment

Intensifying to injectable therapies (2 of 2)

Pharmacologic Approaches to
Glycemic Management:
Standards of Medical Care in
Diabetes - 2021. Diabetes
Care 2021;44(Suppl. 1):S111-
S124
 Highly recommended immunizations for adult patients with diabetes
Vaccine Age group recommendations Frequency

Hepatitis B < 60 years of age; ≥ 60 years of age after discussion with 2 or 3-dose series
care provider

Human papilloma virus ≤ 26 years of age; 27-45 years of age may also be 3 doses over 6 months
vaccinated against HPV after a discussion with their care
provider

Influenza All patients; advised not to receive live attenuated influenza Annual
vaccine

Pneumonia (PPSV-23) 19-64 years of age, vaccinate with Pneumovax 2

≥ 65 years of age, obtain second dose of Pneumovax, at 2

least 5 years from prior Pneumovax vaccine

Pneumonia (PCV-13) 19 – 64 years of age, no recommendation

≥ 65 years of age, without an immunocompromising 3

condition (e.g. CKD), cochlear implant, or cerebrospinal fluid
leak, have shared decision-making discussion with doctor

Tetanus, diphtheria, All adults; pregnant women would have an extra dose Booster every 10 years
pertussis (TDaP)
Zoster ≥ 50 years of age Two-dose Shingrix, even if
previously vaccinated
References
◈ Jameson et. al (2018). Harrison’s Principles of Internal Medicine, 20th edition.
Volume 2

◈ American Diabetes Association (2021). Standard of Medical Care in Diabetes