Diabetes

Diabetes
Esteban Toro Vélez
PGY-1, Internal Medicine
UT Health San Antonio
10/01/2021

Importance of Knowing About Diabetes
● 30.3 million people (9.4%) have in the USA
● Incidence is increasing
○ Aging population and obesity
● Leading cause of vision loss, amputation, ESRD
● Poses a signiﬁcant ﬁnancial burden to individuals and society
● Annual cost of diagnosed diabetes in 2017 was $327 billion
○ $237 billion in direct medical costs
○ $90 billion in reduced productivity
Vijan S. Type 2 Diabetes. Annals of Internal Medicine. 2019;171(9):ITC65-ITC80.
Association A. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S7-S14.

Types of diabetes
Type 1
● 5-10% of cases
● Autoimmune
destruction of
pancreatic cells
● GAD65, Insulin,
tyrosine phosphatases
IA-2 and IA-2B, Zinc
transporter 8 (ZnT8)
● Prone to other disease_
Hashimoto, Graves,
celiac, Addison, vitiligo,
myasthenia gravis,
pernicious anemia
Type 2
● 90-95%
● B-cell death and dysfunction
● Deficient insulin secretion
● Insulin resistance
● Secondary to inflammation
and metabolic stress plus
genetic factors
● “Non-insulin dependent
diabetes”
● DKA is possible: infection,
MI, drugs (steroids,
antipsychotics, SGLT2)
● Insulin resistance may
improve
Others
● Cystic fibrosis related
diabetes
● Post transplantation
diabetes
● Monogenic diabetes
syndromes
● Maturity onset diabetes
of the young
● GDM
Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S15-S33.

“In both type 1 and type 2 diabetes, various genetic and environmental factors can result in the
progressive loss of B-cell mass and/or function that manifests clinically as hyperglycemia. Once
hyperglycemia occurs, patients with all forms of diabetes are at risk for developing the same chronic
complications, although rates of progression may differ”

Why Screen for Diabetes?
● Prevent complications of hyperglycemia
● Diabetes will also affect the management for other comorbidities
● Symptoms: Polyuria, polydipsia, polyphagia, weight loss
● Laboratory: HbA1C, fasting glucose, Glucose tolerance test
https://ilc.peaconline.org/m/1547/p/4824/i/28911

Who Should Be Screened?

Deﬁning Prediabetes

Diagnosis of Diabetes

Which one is better?
● All are equally appropriate for diagnostic screening
● 2h PG diagnose more people with prediabetes and diabetes
● If there is discordance between A1C and glucose values, use FPG and 2H PG
○ Hemoglobinopathies, pregnancy, G6PD, HIV, hemodialysis, recent blood loss, transfusion, EPO.
○ Only plasma glucose should be used
● A1c: Advantages: Greater convenience, less day to day variations

Prevention or Delay of Diabetes
● Obesity is the most important risk factor
● Lack of exercise and smoking
● Losing an average of 4.2kg and exercising,
reduces the risk of developing diabetes by 58%
○ Goal of weight loss 5-10 (7%)
○ Exercise at least 150min/wk
● DPP: Metformin 850mg BID, or lifestyle
interventions or placebo.
○ Lifestyle intervention 58%
○ Metformin 31%
● Metformin: under age 60 with increased risk of
diabetes, who are obese and have at least family
history, low HDL-C
Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S34-S39
https://ilc.peaconline.org/m/1547/p/4824/i/28913.

Eﬀects of Glycemic Control (Microvascular)
DCCT: Diabetes Control and Complications Trial
● 1441 patient with type 1 diabetes
● Usual care (1-2 times insulin) Vs intensive
therapy (frequent monitoring and
adjustment of insulin and insulin 3-4 times a
day)
● Reduction of retinopathy, nephropathy and
neuropathy onset and progression
● Pt with HLD, HTA, CAD excluded; impact on
macrovascular was not signiﬁcant
UKPDS (United Kingdom Prospective Diabetes
Study)
● 5100 with newly diagnosed type 2 DM,
ages 25-65.
● Diet, and if failed, then glyburide, or
metformin, or insulin
● Compared to diet therapy alone, the 3 drugs
reduced microvascular complications
● Each 1% reduction in A1C, decreased
reduced 37% risk of microvascular
complications

Effects of Glycemic Control (Macrovascular)
Accord
● History of cardiovascular event
or significant cardiovascular
risk
● Cardiac outcomes (nonfatal MI,
nonfatal CVA, or cardiovascular
death)
● Intensive (A1C below 6.0) Vs
usual (A1c of 7.0-7.9)
● Terminated prematurely:
Higher mortality in intensive
treatment group
● Non fatal MI were reduced
● Lowering A1C below 7%,
doubles risk of death
Advance
● At least 55, with history of
microvascular or
macrovascular, or at least one
risk factor for vascular disease
● Intensive A1C less than 6.5 or
usual care
● 5 year follow up: Fewer
macrovascular, NO reduction in
macrovascular events
● Hypoglycemia: increased risk
of major macrovascular and
microvascular events,
increased risk of death
VADT (Veterans Affairs Diabetes Trial)
● Poorly controlled diabetes (A1C
avg 9.4)
● Intense goal of A1C 6% or usual
care (goal A1c 1.5% above
intensive control group)
● No early benefits on these
macrovascular outcomes
● After 10 years, fewer major
cardiovascular outcomes

4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S40-S52.

Glycemic Targets
● At least 2 times a year in patient who meet goals
● Quarterly and/or as needed in those
○ Are not meeting goals
○ Therapy has recently been changed
6. Glycemic Targets: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S73-S84.

6. Glycemic Targets: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S73-S84.

Metformin
● Mechanism of action
○ Reduces hepatic gluconeogenesis and glycogenolysis
○ Enhances peripheral glucose uptake
○ Enhances insulin sensitivity
○ Decreases glucose absorption in GI tract
● Reduces A1c by 1.5%
● Low risk hypoglycemia, less weight gain, low cost, reduction in complications
● Administered with largest meal of the day or with breakfast and dinner
● AE: Vit. B12 deﬁciency, lactic acidosis, avoid if EGFR less than 30

SGLT-2 Inhibitors
● Canagliflozin (Invokana), empagliflozin (Jardiance), Dapagliflozin (Farxiga), Ertugliflozin (Steglatro)
● MA: Blocks renal glucose absorption, leads to glycosuria
● Weight loss is common
● Positive cardiovascular benefits, heart failure, CKD
● AE: Genital fungal infections, Fournier's gangrene, dehydration, risk of diabetic ketoacidosis
● Requires renal adjustment

GLP-1 agonists
● Liraglutide (Victoza), Dulaglutide (Trulicity), Semaglutide
● MA: Mimic effects of incretins, delay gastric emptying, improve satiety, weight loss
● Reduces cardiovascular mortality, may reduce progression of CKD
● AE: Nausea, bloating, vomiting, diarrhea
● Black Box: Thyroid C-cell tumors, risk of pancreatitis

DPP-4 inhibitors
● Sitagliptin (Januvia)
● MA: inhibits DPP-4, which is an enzyme that degrades incretins. Leads to increased insulin.
● Less effective than GLP-1
● Do not cause weight gain
● AE: Joint pain, urticaria, angioedema, risk of pancreatitis
● Very expensive

Thiazolidinediones
● Pioglitazone (Actos)
● MA: Sensitize muscle, fat and liver cells to the effects of insulin
● Reduction in plasma glucose and A1c
● Low risk of hypoglycemia
● Effects on microvascular outcomes, unknown
● AE: Fluid retention, concern in patient with heart failure (contraindicated in NYHA III-IV)

Sulfonylureas and Glitineds
Sulfonylureas
● Glyburide, glipizide, glimepiride and
gliclazide
● MA: Stimulate beta cells to produce
insulin
● Can lower HbA1C by 1.5%
● High risk of hypoglycemia and weight
gain
Glitineds
● Nateglinide (Starlix), repaglinide
(Prandind)
● Same mechanism of action
● Dosed with meals
● Useful in those with irregular eating
patterns
● Repaglinide, severe hypoglycemia if
used in conjunction with gemﬁbrozil
● Unknown impact on micro and
macrovascular complications

Alpha-glucosidase inhibitors
● Acarbose (precose), 3x daily, with meals
● MA: reduce intra-intestinal polysaccharides activity, prevents breakdown of CHO’s in simple
sugars
● Lowers A1C by 0.5-0.8
● No weight gain
● AE: GI mainly, diarrhea and ﬂatulence
● Effect on micro and macrovascular complications, unknown

Insulin
● Most effective drug at lowering blood glucose levels
● Indications
○ Patient with weight loss
○ Symptoms of hyperglycemia
○ A1C greater than 10
○ Blood glucose levels above 300
● Risks: Weight gain and hypoglycemia
● No ceiling dose
● Women who are or may become pregnant

Insulin
● Start basal insulin at either 10 units/day or
0.1-0.2ui/kg/day
● Titrate
○ Increase by 2 units every 3 days until FPG
goal is reached (less than 130mg/dl)
○ If hypoglycemia, lower dose by 10/20%
● Over basalization
○ Basal dose greater than 0.5 IU/Kg
○ Elevated bedtime-morning and/or
post/preprandial differential, hypoglycemia
○ High variability

Insulin if A1c above target
● Add GLP-1, if not already in regimen
○ Might need to lower insulin dose
● Add prandial insulin
○ One dose with largest meal or meal with greatest PPG
○ 4 IU a day or 10% of basal insulin dose
○ Increase dose by 1-2 IU or 10-15% twice weekly
○ If A1C below 8, consider lowering the basal dose by 4IU or 10%
○ If hypoglycemia, lower dose by 10/20%
● Still above target
○ Add injection of prandial insulin -- Then basal-bolus regimen

9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S111-S124.

Initiation of Pharmacotherapy
● Monotherapy
○ Usually start with metformin
○ Lifestyle modiﬁcations every visit
○ Start 500mg QD or BID or 850mg daily
○ If tolerated after 1wk, double dose
○ If GI side effects, lower to previous dose
● Dual therapy: If A1C greater than 1.5% above target
● Insulin therapy

Vijan S. Type 2 Diabetes. Annals of Internal Medicine. 2019;171(9):ITC65-ITC80

Ferro E, Elshazly M, Bhatt D. New Antidiabetes Medications and Their Cardiovascular and Renal Benefits. Cardiology Clinics. 2021;39(3):335-351.

Conclusions
● As an internist, it is essential to know about diabetes
● Know when and how to screen
● Know your patient and his comorbidities
● When starting a diabetes medication, know the indications, beneﬁts and adverse events
● Insulin is a good medication, if used appropriately
● Diabetes management is changing

● Vijan S. Type 2 Diabetes. Annals of Internal Medicine. 2019;171(9):ITC65-ITC80.
● Ferro E, Elshazly M, Bhatt D. New Antidiabetes Medications and Their Cardiovascular and Renal Benefits. Cardiology Clinics.
2021;39(3):335-351.
● 1. Association A. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes—2021.
Diabetes Care. 2020;44(Supplement 1):S7-S14
● 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care.
2020;44(Supplement 1):S15-S33.
● https://ilc.peaconline.org/m/1547/p/4824/i/28911
● 3. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care.
2020;44(Supplement 1):S34-S39.
● 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes—2021.
Diabetes Care. 2020;44(Supplement 1):S40-S52.
● 6. Glycemic Targets: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44(Supplement 1):S73-S84.
● 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2021. Diabetes Care.
2020;44(Supplement 1):S111-S124.

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