Type 1 DM

Type 1 DM
• Autoimmune destruction of pancreatic β-cells
• ~90% of patients have markers of immune β-cell
destruction at diagnosis
• (HLA-DR[Human leukocyte antigen-DR], islet cell antibodies,
insulin auoantobodies, or glutamic acid decarboxylase antibodies)
• children & adolescents often have rapid β-cell destruction
& present with ketoacidosis
• may occur at any age
• Known as latent autoimmune diabetes in adults
(LADA)
• slowly progressive
• sufficient insulin secretion to prevent ketoacidosis for many
years

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Type 1 DM Pathogenesis
1. Preclinical period
• immune markers
present
• β-cell destruction
2. Hyperglycemia
• 80 to 90% of β-
cells destroyed
3. Transient remission
— honeymoon phase
— (remaining 10% of β-cell function à blood glucose levels are easier to
control and smaller amounts of insulin are required)
4. Established disease
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Management
• Lifestyle
• Pharmacologic
Lifestyle Management

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Lifestyle Management
• Lifestyle management is a fundamental aspect of diabetes care and
includes
• diabetes self-management education and support (DSMES),
• medical nutrition therapy (MNT),
• physical activity,
• smoking cessation counseling,
• psychosocial care.

• Patients and care providers should focus together on how to optimize

lifestyle from the time of the initial comprehensive medical evaluation,
throughout all subsequent evaluations and follow-up, and during the
assessment of complications and management of comorbid conditions in
order to enhance diabetes care.
Diabetes Self-Management Education & Support (DSMES): Recommendations
• In accordance with the national standards for DSMES, all people with diabetes should
participate in DSME to facilitate the knowledge, skills, and ability necessary for diabetes self-
care and in DSMS to assist with implementing and sustaining skills and behaviors needed for
ongoing self-management. B
• There are four critical times to evaluate the need for DSMES:
• at diagnosis,

• annually,

• when complicating factors arise,

• when transitions in care occur. E

• Facilitating appropriate diabetes self-management and improving clinical outcomes, health

status, and quality of life are key goals of DSMES to be measured and monitored as part of
routine care. C
• Effective DSMES should be patient centered, may be given in group or individualized settings
or using technology, and should help guide clinical decisions. A
• Because DSMES can improve outcomes and reduce costs B, adequate reimbursement by third-
party payers is recommended. E
Goals of Medical Nutrition Therapy (MNT)
1. To promote and support healthful eating patterns, emphasizing a
variety of nutrient-dense foods in appropriate portion sizes, to
improve overall health and to:
• Achieve and maintain body weight goals
• Attain individualized glycemic, blood pressure, and lipid goals
• Delay or prevent the complications of diabetes
2. To address individual nutrition needs based on personal & cultural
preferences, health literacy & numeracy, access to healthful foods,
willingness and ability to make behavioral changes, & barriers to
change
3. To maintain the pleasure of eating by providing non-judgmental
messages about food choices
4. To provide an individual with diabetes the practical tools for developing
healthful eating patterns rather than focusing on individual
macronutrients, micronutrients, or single foods
NUTRITION THERAPY AND TYPE 1 DM
• For patients with Type 1 diabetes taking fixed doses of insulin, a meal plan is
designed to provide adequate carbohydrates timed to match the peak action of
exogenously administered mealtime insulin.

• Regularly scheduled meals and snacks should contain consistent carbohydrate

amounts, which are required to prevent hypoglycemic reactions.

• Note: newer insulins and insulin regimens provide much more flexibility in the
amount and timing of food intake. Patients who are taught to count carbohydrates
can inject rapid- or short-acting insulin doses designed to match their anticipated
intake. Integration of food intake, physical activity, and insulin dose is critical and
discussed extensively in the cases that follow.
• When patients are taught to estimate the grams of carbohydrate in a meal, they are given the
following guideline: One carbohydrate serving = 1 starch or 1 fruit or 1 cup milk = 15 g
carbohydrate.
• Patients vary with regard to their insulin-to-carbohydrate ratio throughout time and
throughout the day; however, a typical starting point is 1 unit/15 g carbohydrate.
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Physical activity
• Exercise
• improves insulin resistance, glycemic control
• reduces CV risk (HTN and elevated serum lipids)
• helps with weight loss or maintenance
• improves well-being

• Patients without contraindications

• > 150 min/week moderate-intensity aerobic exercise
• resistance training for 30 min 3 times/week

• Start exercise slowly in previously sedentary patients.

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Nonpharmacologic Therapy
• Evaluation for exercise
• routine CAD screening not recommended for asymptomatic patients
• high risk patients may need CV evaluation
• complications can require activity restrictions
• retinopathy: vigorous aerobic or resistance exercise contraindicated
• peripheral neuropathy: non-weight bearing activities only
• autonomic neuropathy: cardiac investigation prior to starting any activity

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Nonpharmacologic Therapy
• Psychological assessment and care
• Determining the patient’s attitude regarding DM, expectations of medical
management and outcomes, mood and affect, general and diabetes quality
of life and financial, social and emotional resources.

• Immunization
• Provide influenza vaccine annually to all diabetic patients ≥6 months of
age
• Administer pneumococcal polysaccharide vaccine to all diabetic patients
≥2 years
– One-time revaccination recommended for those >64 years previously immunized at
<65 years; if administered >5 years ago
– Other indications for repeat vaccination: nephrotic syndrome, chronic renal
disease, immunocompromised states
• Administer hepatitis B vaccination to unvaccinated adults with diabetes
who are aged 19 through 59 years
• Consider administering hepatitis B vaccination to unvaccinated adults with
diabetes who are aged ≥60 years
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Pharmacologic Therapy For Type 1 Diabetes:
Recommendations
• Most people with T1DM should be treated with multiple daily injections of
prandial insulin and basal insulin or continuous subcutaneous insulin
infusion (CSII). A

• Most individuals with T1DM should use rapid-acting insulin analogs to

reduce hypoglycemia risk. A
• Consider educating individuals with T1DM on matching prandial insulin
doses to carbohydrate intake, premeal blood glucose levels, and
anticipated physical activity. E
• Individuals with T1DM who have been successfully using CSII should have
continued access to this therapy after they turn 65 years of age. E
Insulin
• Anabolic & anti-catabolic hormone
• Necessary for carbohydrate, protein & fat metabolism
• Required for all type 1 DM patients
• Recommended for type 2 DM patients that do not achieve glycemic control
with PO anti-diabetic agents
• Insulin strengths
• 100 units/mL (U-100)
• 500 units/mL (U-500) - only available in regular insulin

• Originally derived from bovine & porcine pancreas

• All human insulin in the US now made exclusively by recombinant DNA
(rDNA) technology
• Recombinant insulin analogs also available via modification of human
insulin molecules
• synthesized to overcome problems of human insulin related to onset of action,
duration of action, and absorption
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Insulin types and properties
• The route of administration for insulin is primarily via SC injection.
• Regular insulin, a solution, can be administered by any parenteral route: IV, intramuscularly
(IM), or subcutaneously (SC).
• Most other injectable insulins are only to be used SC with the exception of insulin aspart
and insulin lispro which may be used via IV route if they are first diluted.
• Afrezza (insulin human) is the only insulin currently available as a powder for inhalation.

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Empiric insulin doses
General guidelines provide only estimates
patients respond differently
Estimating Total Daily Insulin Requirements
These are initial doses only; they must be refined using SMBG results. Patients may be
particularly resistant to insulin if their blood glucose concentrations are high (glucose
toxicity); once glucose concentrations begin to drop, insulin requirements often decrease
precipitously.
The weight used is actual body weight. Insulin dose requirements can change dramatically
over time depending on circumstances (e.g., a growth spurt, modest weight gain or loss,
illness).
Type 1 diabetes
Initial dose 0.3–0.5 unit/kg
Honeymoon phase 0.2–0.5 unit/kg
With ketosis, during illness, during 1.0–1.5 units/kg
growth
Type 2 diabetes (doses vary depending on degree of insulin resistance)
With insulin resistance 0.7–1.5 units/kg
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Estimating Basal Insulin Requirements
These are empiric doses only and should be adjusted using appropriate SMBG results (fasting
or premeal).
Basal insulin requirements:
vary throughout the day, often increasing during the early morning hours.
are approximately 50% of total daily insulin needs.
influenced by the presence of endogenous insulin, the degree of insulin resistance, and
body weight.

Estimating Premeal Insulin Requirements

The “500 rule” estimates the number of grams of carbohydrate that will be covered by 1 unit
of rapid-acting insulin. The rule is modified to the “450 rule” if using regular insulin.
500/total daily dose of insulin (TDD) = number of grams covered

Example: For a patient using 50 U/day, 500/50 = 10. Therefore, 10 g

carbohydrate would be covered by 1 unit of insulin lispro, glulisine, or aspart.
This equation works very well for type 1 patients in estimating their premeal
insulin requirements.
Because patients with type 2 diabetes have insulin resistance, the rule may
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underestimate their insulin requirements.
Determining the “Correction Factor”
Supplemental doses of rapid-acting insulin are administered to acutely lower glucose
concentrations that exceed the target glucose concentration.
These doses must be individualized for each patient and again are based on the
degree of sensitivity to insulin action.
For example, if the premeal or bedtime blood glucose target is 140 mg/dL and
the patient's value is 190 mg/dL, additional units of insulin might be added to
the premeal dose or an additional supplemental bedtime dose of rapid-acting
insulin might be given.

The correction factor determines how far the blood glucose drops per unit of insulin
given and is known as the “1700 rule”. For regular insulin, the rule is modified to the
“1500 rule.” The equation is as follows:
1700/TDD = point drop in blood glucose per unit of insulin

Example: If a patient uses 28 U/day of insulin, their correction factor (or insulin
sensitivity) would be 1700/28 = 60 mg/dL. Therefore, the patient can expect a 60
mg/dL drop for every unit of rapid acting insulin administered. Patients with a
higher sensitivity factor have lower insulin requirements. Individuals with a lower
sensitivity factor (higher insulin requirements) typically achieve a smaller reduction 18
in blood glucose per unit of insulin.
T1DM: Pramlintide
• FDA approved for T1DM
• Amylin analog
• Delays gastric emptying, blunts pancreatic glucose secretion,
enhances satiety
• Induces weight loss, lowers insulin dose
• Requires reduction in prandial insulin to reduce risk of severe hypos
• Decreased preprandial insulin dose by 50%
Pharmacologic Approaches to Glycemic Treatment:
Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
T1DM: Investigational Agents
• Metformin
• Incretin-Based Therapies
• Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists
• Dipeptidyl Peptidase 4 (DPP-4) Inhibitors
• Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

Pharmacologic Approaches to Glycemic Treatment:

Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
Assessment of Glycemic Control
• Two primary techniques are available for health providers
and patients to assess the effectiveness of a management
plan on glycemic control:
1. Patient self-monitoring of blood glucose (SMBG)
2. A1C
• Continuous glucose monitoring (CGM) also has an
important role in assessing the efficacy and safety of
treatment in subgroups of patients with T1DM and in
selected patients with T2DM.
• Data indicate similar A1C and safety with the use of CGM
compared with SMBG.
Glycemic Targets:
Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S55-S64
Glucose Monitoring: SMBG
Recommendations
• Most patients using intensive insulin regimens
(multiple-dose insulin or insulin pump therapy)
should perform SMBG:
• Prior to meals and snacks
• At bedtime
• Occasionally postprandially
• Prior to exercise
• When they suspect low blood glucose
• After treating low blood glucose until they are
normoglycemic
• Prior to critical tasks such as driving
• So, at least three times daily for type 1 diabetes
Hypoglycemia management
1- Hypoglycemia
• low blood sugar,
• defined clinically as a blood glucose level of less than 50 mg/dL.
• Individuals with DM can experience symptoms of hypoglycemia at varying blood glucose
levels.
• Patients who have regular blood glucose levels as high as 300 to 400 mg/dL may experience
symptoms of hypoglycemia once blood glucose levels are lowered to the middle to upper 100 mg/dL
range.
• Most people whose blood glucose levels are controlled adequately may experience symptoms when
levels fall below 70 mg/dL.

• Symptoms include: tremor (shakiness), sweating, fatigue, hunger,

headaches, and confusion. Signs: tachycardia
• Common causes include:
• delayed or inadequate amounts of food intake, especially carbohydrates,
• excessive doses of medications (e.g., sulfonylureas and insulin),
• exercising when insulin doses are reaching peak effect,
• inadequately adjusted drug therapy in renally or hepatically impaired patients.
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• For patients with hypoglycemia experiencing a loss of
consciousness,
• a glucagon emergency kit should be administered by
intramuscular or subcutaneous route,
• Glucagon dose:
• for a child younger than 5 years of age is 0.25 to 0.5 mg;
• for children 5 to 10 years of age, 0.5 to 1 mg;
• for patients older than 10 years, 1 mg)
• If glucagon is unavailable à IV glucose
• emergency medical personnel should be contacted.
• The patient should be rolled onto his or her side to prevent
aspiration since many patients receiving the glucagon
injection will vomit.

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• Initiating Insulin Therapy for Type 1 Diabetes
• all patients with type 1 diabetes require insulin, which should ideally be managed with an
endocrinologist
• most patients should be treated with either multiple daily insulin injections of prandial and basal
insulin (basal-bolus therapy) or continuous subcutaneous insulin infusion (insulin pump) (ADA
Grade A)
• insulin preparations range from rapid- to ultra long-acting and include human and human analogs
• onset, peak, and duration vary
• most common regular insulin and insulin analog concentration is 100 units/mL (U-100)
• more concentrated insulins exist (such as U-200 aspart and degludec, U-300 glargine, and U-500 regular),
some of which have significantly different kinetics than the same medication at U-100 concentration (such as
U-300 glargine having potentially lower hypoglycemia risk than U-100 glargine)
• insulin dosing regimens for type 1 diabetes include
• basal-bolus therapy, defined as basal insulin with either multiple daily injections or continuous subcutaneous
insulin infusion (CSII) plus boluses with meals/snacks intended to mimic physiologic insulin secretion (also
called intensive insulin therapy or multiple daily injection therapy)
 • premixed insulin therapy, defined as premixed, fixed dose formulations of long- or intermediate-acting insulins plus rapid-
or short-acting insulins to approximate basal-bolus regimen but with fewer injections and less flexibility
• use rapid-acting insulin analogs to reduce risk of hypoglycemia (ADA Grade A)
• in general, insulin requirements can be estimated based on weight with typical regimens consisting of doses
ranging 0.4-1 units/kg/day (administered in divided doses with about 50% of total daily dose given as basal
insulin and 50% as prandial)
• higher amounts are required during puberty, pregnancy, and acute illness
• a starting total daily dose of 0.5 units/kg/day may be appropriate
• sensitivity to insulin varies widely, so dosing must be adjusted on basis of individual response to therapy
• when adjusting insulin doses, depending on degree of hypo- or hyperglycemia
and the patient's insulin sensitivity, it is reasonable to increase or decrease
insulin dose by 10%-20% and wait 3-5 days to assess response
• educate patients on dosing prandial insulin in context of carbohydrate intake, premeal blood glucose, and expected physical
activity (ADA Grade C)
• early in diagnosis of type 1 diabetes, patients may have lower insulin needs due to residual production of insulin from
remaining beta cells; therefore, insulin requirements may be at the lower end of range
• glycemic goals
• HbA1c < 7% (53 mmol/mol) is reasonable goal for many nonpregnant adults without significant hypoglycemia
(ADA Grade A), but goal should be individualized based on
• duration of diabetes
• age and life expectancy
• important comorbidities
• presence of known cardiovascular disease or advanced microvascular complications
• risks associated with hypoglycemia and other adverse drug effects
• other individual considerations (such as patient preferences and abilities, resources, and support system)
• more stringent target, such as HbA1c < 6.5% (48 mmol/mol), may be reasonable if it can be achieved without
significant hypoglycemia or other adverse effects of treatment (such as polypharmacy) for selected patients
(ADA Grade C), such as those with
• short duration of diabetes
• long life expectancy
• no significant cardiovascular disease
• less stringent target, such as HbA1c < 8% (64 mmol/mol), may be appropriate for patients with (ADA Grade B)
• history of severe hypoglycemia
• limited life expectancy
• harms of treatment likely to outweigh the benefits