Type 1 & 2 Diabetes Mellitus

• Diabetes mellitus (DM) is characterized by inadequate control of blood glucose levels.

Cardinal Signs of DM

• Polydipsia (excessive thirst)
• Polyuria (frequent urination)
• Polyphagia (excessive hunger)

Types of DM

• Type 1 DM involves low or absent insulin, positive beta-cell autoantibodies, and ketosis.
• Type 2 DM results from a progressive insulin secretory defect coupled with insulin resistance.
• Type 1 - no insulin; Type 2 - insulin that doesn't work properly.

Screening Guidelines

• The American Association of Clinical Endocrinologists, American Academy of Family Physicians, Diabetes Australia, Diabetes UK, and the Canadian Task Force on Preventive Health Care suggest diabetes screening for individuals with risk factors only.

Classic Presentation

• Most patients are asymptomatic and identified through routine lab evaluations detecting hyperglycemia.
• Symptoms include polydipsia, polyuria, nocturia, blurred vision, infrequent weight loss, fatigue, slow wound healing, frequent infections, and numbness/tingling in extremities.
• Polyuria is common when serum glucose exceeds 180mg/dL, the renal threshold for glucose.
• Type 2 diabetes patients might have no or subtle symptoms lasting for weeks, months, or years before detection.

Type 2 DM: Pathophysiology

• Insufficient insulin secretion and increased insulin resistance are key features.
• The causes include genetic predisposition and environmental factors like viruses, microbiome, physical activity, and diet.
• Inflammation and autoimmunity can lead to beta-cell destruction
• Inflammation and metabolic stress can lead to beta-cell dysfunction

Complications of DM

• Microvascular: retinopathy, nephropathy, neuropathy
• Macrovascular: coronary artery disease, peripheral arterial disease, stroke

Type 2 DM

• Type 2 DM was once known as "non-insulin-dependent diabetes" or "adult-onset diabetes".
• It accounts for 90-95% of all cases.
• Individuals typically exhibit insulin resistance and relative rather than absolute insulin deficiency.

DM Screening in Asymptomatic Adults: Risk Factors

• Overweight or obese individuals (BMI >25, or >23 for Asian Americans) with additional factors.
• Physical inactivity, first-degree relative with diabetes, high-risk race/ethnicity (e.g., African American, Latino, Native American, Pacific Islander)
• History of delivering a baby weighing 9 lbs or GDM diagnosis.
• Hypertension (>140/90 mmHg or on therapy).
• HDL cholesterol ≤35 mg/dL or triglycerides ≥250 mg/dL (2.82 mmol/L).
• Polycystic ovary syndrome, A1C ≥5.7%, IGT, or IFG, clinical conditions linked to insulin resistance, or history of CVD

Screening Criteria

• Testing starts at age 45 for all patients.
• If results are normal, repeat testing at least every 3 years, with more frequent testing if prediabetes is present.

Diagnostic Tests

• Serum Glucose: normal (<100 mg/dL), prediabetes (100-125 mg/dL), diabetes (≥126 mg/dL on two occasions).
• HbA1C: normal (<5.7%), prediabetes (5.7-6.4%), diabetes (>6.5%).
• Oral Glucose Tolerance: normal (<140mg/dL), prediabetes (140-199mg/dL), diabetes (>200mg/dL after 2 hours).

Additional Tests

• Urinalysis: Checks for proteinuria, glucosuria
• C-peptide: normal (0.51-2.72 ng/dl), T1DM (<0.51 ng/dl), T2DM (>2.72 ng/dl)
• Fasting lipid profile, liver function tests, spot urinary albumin-to-creatinine ratio, serum creatinine, and estimated GFR should be performend if not performed/available in the last year.
• TSH in patients with dyslipidemia or women aged >50

Comprehensive Medical Evaluation Components

• Age/characteristics of diabetes onset, nutritional status, weight history, physical activity habits, nutrition education, and behavioral support.
• Presence of comorbidities, psychosocial problems, dental disease, and depression (using PHQ-2, PHQ-9 if PHQ-2 is positive).
• Screen for diabetes distress using DDS or PAID-1
• History of smoking, alcohol/substance use, diabetes education, self-management, and support history/needs

Physical Examination

• Height, weight and BMI for growth and pubertal development in children and adolescents
• Height, weight, and BMI
• Blood pressure assessment, including orthostatic measurements.
• Eye examination (fundoscopy).
• Oral cavity inspection for gum disease, fungal infections, or lesions.
• Neck palpation for thyroid assessment.
• Cardiac evaluation: HR, rate, rhythm, murmurs, etc.
• Skin assessment for irritation, infection, redness, ulcers, dryness, acanthosis nigricans.
• Feet examination: pulses, reflexes, sensation, overall skin condition.

Glycemic Targets: Non-Pregnant Adults

• HgbA1C: Less than 7.0%
• Pre-prandial capillary plasma glucose: 80-130 mg/dL
• Peak postprandial capillary plasma glucose (1-2 hours after meals): Less than 180 mg/dL

Stringent AIC Goals, (6.5%) are appropriate for individuals with:

• Short duration of diabetes
• Type 2 diabetes managed with lifestyle or metformin alone
• Long life expectancy
• No significant cardiovascular issue

Less Stringent A1C Goals, (8%) are appropriate for:

• History of severe hypoglycemia
• Limited life expectancy
• Advanced microvascular or macrovascular complications
• Extensive comorbid conditions
• Long-standing diabetes where the general goal is difficult to attain despite self-management education

Glycemic Testing Frequency

• A1C: At least twice a year for patients meeting treatment goals with stable glycemic control and quarterly for those whose therapy changes or are not meeting glycemic goals.
• Continuous Glucose Monitoring (CGM) recently approved by the U.S. Food and Drug Administration (FDA) for use in those over 18 years of age

Factors Affecting A1C Goals

• When dicussing AIC goals consider age, disease duration, and life expectancy.
• Risk for hypoglycemia and presence of comorbid conditions.
• Consider the degree of social support and attitude/ability for adhering to treatment
• A1C goals should be as close to normal as safe.
• Younger/ newly diagnosed patients should have stricter AIC goals.

Type 2 DM Treatment

• Treatment should be based on an agent/agent that minimizies hypoglycemia/ weight gain
• Consider comorbid CV and renal risk factors
• First line therapy is Metformin (500mg - 2,000mg/day) combined with lifestyle modifications (weight loss, increased physical activity, and healthy eating).

Medications for Type 2 DM

• Biguanide (Metformin): 1.0-2.0% A1C reduction, neutral weight, not associated with hypoglycemia
• SGLT2 Inhibitor - canagliflozin (Invokana): less than 1.0% A1C reduction, weight loss
• DPP-4 Inhibitor - sitagliptin (Januvia): 0.5-0.8% A1C reduction, weight neutral, not associated with hypoglycemia
• TZD: pioglitazone (Actos):0.5-1.0% A1C reduction, causes weight gain, not associated with hypoglycemia
• SU: glimepiride (Amaryl): 1.0-2.0% A1C reduction, causes weight gain and hypoglycemia
• GLP-1 RA semaglutide (Onglyza): 0.6-1.5% A1C reduction, weight loss, not associated with hypoglycemia
• Glinides - nateglinide (Starlix): 0.4-0.9% A1C reduction, causes weight gain and hypoglycemia

Treatment Strategies

• Initiate monotherapy
• Add treatments in a step-wise approach, if patients do not achieve their AIC goals.
• Initiate combination therapy with AIC greater than or equal to 9, or greater than 7 with monotherapy.
• Do not bring glucose down to fast, could cause hypoglycemia.

Choosing a Medication

• Choose medication based on patient morbidities and cost.
• Sulfonaurea is cheap but associated with hypoglycemia and weight gain.
• Evaluate treatment resposnes every 3 months.

Addressing Treatment Goals

• Address both Fasting Plasma (FPG) and postprandial Glucose (PPG) to achieve A1C goals.
• At higher A1C levels, FPG drives hyperglycemia, but PPG predominates when AIC drops below 7.5%.
• Basal insulin targets FPG (50 to 60 units/day).

Non-Pharmacologic Interventions

• Exercise at least 150 minutes/week of moderate-intensity aerobic activity (50-70% of maximum heart rate)
• Spread activity over ≥3 days/week with no more than 2 consecutive days without exercise.
• Resistance training ≥2 times/week.
• Reduce sedentary time by breaking up periods >90 minutes.
• Avoid alcohol and smoking (including e-cigarettes).
• Lose 5-10% of initial body weight.
• Seek Medical Nutrition Therapy (MNT): 3 visits with a registered dietician at diagnosis and ongoing semi-annual follow-up visits.

Follow-Up Care

• Follow-up every 3 months is required during initial treatment with lifestyle modifications only.
• If treated with medication, check A1C every 3 months until goal (<7%) is reached, then every 3-6 months.

Tests and Referrals

• Obtain an annual lipid profile, serum creatinine, ECG, and TSH.
• Foot inspection each visit or referral to podiatry if needed.
• Get age-appropriate immunizations (influenza, pneumonia).
• Refer an annual total urinary protein check once microalbuminuria is present; then perform total urinary protein assessments.

Screenings for Comorbid Conditions

• Screen for coronary heart disease (BP, fasting lipid profile, smoking history).
• EKG for sedentary adults >50 before starting exercise program
• Check for fatty liver disease, hearing impairment, obstructive sleep apnea and get a dental screening/periodontal disease
• Check for cognitive impairment, depression, fractures, and renal impairment
• Perform an annual eye exam.
• Screen for cancer (liver, pancreas, endometrium, colon/rectum, breast, and bladder).

Referrals/Consultations

• Ophthalmologist (annual dilated eye exam)
• Plan family with women of reproductive age.
• Registered dietitian (MNT)
• Endocrinologist for persistent hyperglycemia despite the use of at least 3 oral agents and/or insulin for Type 2 DM, and for Type 1 DM.
• Schedule diabetes self-management education (DSME) and diabetes self-management support (DSMS)
• Get a dentist for comprehensive dental and periodontal examination and a podiatrist.
• Seek mental health professional, if indicated.

Comprehensive Medical Evaluation

• Review previous treatment regimens and response to therapy (A1Carecords)
• Review results of glucose monitoring and patient's use of data
• Keep track of any diabetic ketoacidosis frequency, severity, and cause, hypoglycemia episodes, awareness, and frequency and causes. History of increased blood pressure, increased lipids, and tobacco use
• Microvascular complications: retinopathy, nephropathy, and neuropathy (sensory, including history of foot lesions; autonomic, including sexual dysfunction and gastroparesis)
• Macrovascular complications: coronary heart disease, cerebrovascular disease, and peripheral arterial disease