Diabetes Management and NAFLD/NASH

Improving Care and Promoting Health in Populations

• A multifaceted approach encompassing patient-level, system-level, and policy-level interventions is crucial for enhancing population health in the context of diabetes.

Patient-Level

• Minimize therapeutic inertia in diagnosis and treatment.
• Align with evidence-based treatment guidelines.
• Address social determinants of health.
• Foster shared decision-making that considers individual preferences, prognoses, comorbidities, and financial factors.

System-Level

• Foster a quality-oriented culture to improve safety, timeliness, effectiveness, equity, and person-centeredness through system-based approaches.
• Leverage patient registries and electronic health records for quality enhancement in diabetes care.
• Use collaborative, multidisciplinary health care teams for diabetes care delivery.
• Incorporate telehealth alongside in-person visits to expand access to quality diabetes care.
• Ensure access to diabetes self-management education and support, using both professional and community-based resources.
• Evaluate socioeconomic and linguistic barriers to diabetes management and care, and facilitate referrals to local community resources when needed.

Policy-Level

• Ensure access to health insurance with adequate coverage for all aspects of diabetes management, including medications, supplies/equipment, technology, and medical care.
• Ensure access to health care professionals with expertise in diabetes management.

Diagnostic Tests for Diabetes

• Diagnostic criteria include A1C, fasting plasma glucose, 2-hour glucose value during a 75-g oral glucose tolerance test, and random glucose value with classic hyperglycemia symptoms/hyperglycemic crisis.

A1C

• Prediabetes: 5.7-6.4% (39-47 mmol/mol)
• Diabetes: ≥6.5% (≥48 mmol/mol)

Fasting Plasma Glucose

• Prediabetes: 100-125 mg/dL (5.6-6.9 mmol/L)
• Diabetes: ≥126 mg/dL (≥7.0 mmol/L)

2-hour glucose value during a 75-g oral glucose tolerance test

• Prediabetes: 140-199 mg/dL (7.8–11.0 mmol/L)
• Diabetes: ≥200 mg/dL (≥11.1 mmol/L)

Random glucose value with classic hyperglycemia symptoms/hyperglycemic crisis

• Diabetes: ≥200 mg/dL (≥11.1 mmol/L)

Additional Information on Diabetes Diagnosis

• There is insufficient evidence to support the use of continuous glucose monitoring for screening or diagnosing prediabetes or diabetes.
• In the absence of unequivocal hyperglycemia (e.g., hyperglycemic crisis), diagnosis of type 2 diabetes requires confirmatory testing, which can be a different test on the same day or the same test on a different day.
• Marked discordance between A1C and repeated blood glucose measurements should raise the possibility of a problem or interference with either test.

Classification of Diabetes

• Classification of diabetes type is not always straightforward at presentation, and misdiagnosis is common.

Types of Diabetes

• Includes type 1 diabetes (idiopathic or autoimmune β-cell destruction), type 2 diabetes (non-autoimmune progressive loss of adequate β-cell insulin secretion frequently on the background of insulin resistance and metabolic syndrome), gestational diabetes mellitus (GDM; detected at 24-28 weeks of gestation in individuals without previously identified diabetes or high-risk glucose metabolism), and diabetes from other causes (e.g., monogenic diabetes syndromes, diseases of the exocrine pancreas, and drug- or chemical-induced diabetes).

Screening Criteria for Prediabetes and Type 2 Diabetes

• Screening for prediabetes and type 2 diabetes should be performed in asymptomatic adults with an informal assessment of risk factors or a validated risk calculator.

Informal Risk Factor Assessment for Prediabetes and Type 2 Diabetes

• Includes everyone ≥35 years of age, people with prior GDM, history of prediabetes, and people with HIV, exposure to high-risk medicines, or a history of pancreatitis.
• Adults (≥18 years of age) with overweight or obesity (BMI ≥25 kg/m² or ≥23 kg/m² in Asian American individuals) who have one or more of the following risk factors: First-degree relative with diabetes, high-risk race/ethnicity, history of cardiovascular disease, hypertension (≥130/80 mmHg or on therapy for hypertension), polycystic ovary syndrome, HDL cholesterol <35 mg/dL (<0.9 mmol/L) and/or triglycerides >250 mg/dL (>2.8 mmol/L), physical inactivity, and other clinical conditions associated with insulin resistance.

Clinical Notes for Diabetes Screening

• If results are normal, repeat screening at least every 3 years (annually for those with prediabetes), or sooner with symptoms or changes in risk.
• Risk-based screening for prediabetes or type 2 diabetes 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 ≥95th percentile) who have one or more risk factors for diabetes.

Additional Screening Guidelines

• An altered relationship between A1C and glycemia, acute pancreatitis, cystic fibrosis, posttransplantation status, possible monogenic diabetes, and therapy with certain medications.

An Altered relationship between A1C and glycemia

• Clinical tips: A mismatch between A1C and glycemia could be caused by some hemoglobin variants, pregnancy (second and third trimesters and the postpartum period), glucose-6-phosphate dehydrogenase deficiency, HIV, hemodialysis, recent blood loss or transfusion, anemia, or erythropoietin therapy.
• People with HIV should be screened for diabetes and prediabetes before and 3-6 months after starting or changing antiretroviral therapy, and annually if initial results are normal.
• Best test: Fasting plasma glucose.

Acute Pancreatitis

• Clinical tips: Screen for diabetes 3-6 months after an episode of acute pancreatitis and annually thereafter.
• Best test: Any standard test for diagnosing diabetes.

Cystic Fibrosis

• Clinical tips: Annual screening should begin by the age of 10 years in all people with cystic fibrosis not previously diagnosed with cystic fibrosis-related diabetes.
• Best test: Oral glucose tolerance test.

Posttransplantation Status

• Clinical tips: Screen for hyperglycemia after organ transplantation. Posttransplantation diabetes mellitus should be diagnosed when the individual is stable on immunosuppressive therapy and free of acute infections.
• Best test: Oral glucose tolerance test.

Possible Monogenic Diabetes

• Clinical tips: Suspect monogenic diabetes in people diagnosed with diabetes in the first 6 months of life and in children and young adults with atypical characteristics of type 1 or type 2 diabetes, who often have a family history of diabetes in successive generations (suggestive of an autosomal dominant pattern of inheritance).
• Best test: Any standard test for diagnosing diabetes plus appropriate genetic testing.

Therapy with Certain Medications

• Clinical tips: Consider screening people for prediabetes or diabetes if they are on certain medications known to increase diabetes risk, such as glucocorticoids, statins, thiazide diuretics, some HIV medications, and second-generation antipsychotic medications.
• Best test: Any standard test for diagnosing diabetes.

Screening for Type 2 Diabetes

• Lab testing is safe and cost-effective
• Screening presents an opportunity to address cardiovascular risk factors (e.g., hypertension and dyslipidemia).
• How to screen: Conduct an informal assessment of risk factors or use an assessment tool such as the ADA risk test or consider diagnostic testing based on assessment results.
• When to screen: Monitor people with prediabetes at least annually and screen those without prediabetes with normal results at least every 3 years.
• Screen after the onset of puberty or after age 10 in children/adolescents with overweight (BMI ≥85th percentile) or obesity (BMI ≥95th percentile) & at least one risk factor.
• Screen with symptoms suggestive of diabetes or changes in risk.

Diet and Physical Activity Recommendations for Adults at Risk for Type 2 Diabetes

• A healthy eating pattern emphasizes whole grains, legumes, nuts, fruits, and vegetables and minimizes refined and processed foods.
• Includes a variety of healthy eating patterns like Mediterranean-style, low-carbohydrate, vegetarian or plant-based, and DASH (Dietary Approaches to Stop Hypertension).
• Regular physical activity is defined as ≥150 min/week of moderate-intensity physical activity, such as brisk walking with the option of resistance or strength training; break up prolonged sedentary time.

What is the Diabetes Prevention Program?

• Demonstrated that intensive lifestyle intervention could reduce the risk of type 2 diabetes by 58% over 3 years.
• The two major goals of the DPP intensive lifestyle intervention were to achieve and maintain ≥7% weight loss and ≥150 min of moderate-intensity physical activity, such as brisk walking, per week.
• Technology-assisted programs using smartphones, web apps, and telehealth platforms can effectively deliver the DPP lifestyle change program, overcoming barriers, especially for low-income and rural individuals.

Person-Centered Care Goals For Individuals at Risk of Type 2 Diabetes

• Important to weigh the individualized risks and benefits of interventions
• Facilitate weight management in those with overweight or obesity
• Minimize progression of hyperglycemia
• Reduce cardiovascular risk

Consider More Intensive Approaches for Individuals At High Risk of Progression to Diabetes

• BMI ≥35 kg/m²
• Higher glucose levels (e.g., fasting plasma glucose 110-125 mg/dL [6.1–6.9 mmol/L], 2-h post-challenge glucose 173-199 mg/dL [9.6–11 mmol/L], and A1C ≥6.0% [42 mmol/mol])
• History of gestational diabetes mellitus

Medications That can be Prescribed to Adults for Prevention of Type 2 Diabetes

• Food and Drug Administration has not approved any drugs for diabetes prevention
• Metformin has the strongest evidence base for diabetes prevention.

Who Should be Considered for Metformin Therapy to Prevent Type 2 Diabetes

• Adults aged 25-59 years with a BMI ≥35 kg/m²
• Individuals with higher fasting plasma glucose (e.g., ≥110 mg/dL [≥ 6 mmol/L])
• Those with higher A1C (e.g., ≥6.0% [≥42 mmol/mol])
• Individuals with a history of gestational diabetes mellitus

What Parameters Should Be Monitoring in People On Metformin Therapy

• Vitamin B12 should be measured periodically, especially in those with anemia or peripheral neuropathy.

Screening for Type 1 Diabetes

• Screen using autoantibodies
• In people with preclinical type 1 diabetes, monitor for disease progression using A1C approximately every 6 months and 75-g oral glucose tolerance test (i.e., fasting and 2-h plasma glucose) annually; modify frequency of monitoring based on individual risk assessment based on age, number and type of autoantibodies, and glycemic metrics.

Medication to Delay the Onset of Type 1 Diabetes

• Teplizumab-mzwv infusion to delay the onset of symptomatic type 1 diabetes should be considered in selected individuals who are ≥8 years of age and have stage 2 type 1 diabetes.

Staging of Type 1 Diabetes

• Characterized by autoimmunity with normoglycemia which is presymptomatic
• Multiple islet autoantibodies
• No IGT or IFG

Stage 2

• Characterized by autoimmunity with dysglycemia which is presymptomatic
• Islet autoantibodies (usually multiple)
• Dysglycemia: IFG and/or IGT
• FPG 100-125 mg/dl (5.6-6.9 mmol/L)
• 2-h PG 140-199 mg/dl (7.8-11.0 mmol/L)
• A1C 5.7-6.4% (39-47 mmol/mol) or ≥10% increase in A1C

Stage 3

• Characterized by autoimmunity with overt hyperglycemia which is symptomatic
• Autoantibodies may become absent
• Diabetes by standard criteria

Does Statin Therapy Increase the Risk of Developing Type 2 Diabetes

• Statin therapy may slightly elevate type 2 diabetes risk in high-risk individuals.
• In primary and secondary prevention of cardiovascular disease, statin benefits outweigh diabetes risk.
• Discontinuing statins based on concerns about increased diabetes risk is not advised.

Does Pioglitazone Have a Role in Secondary Cardiovascular Prevention in People at Risk for Type 2 Diabetes

• Pioglitazone could reduce stroke and myocardial infarction risks in people with a history of stroke and evidence of insulin resistance or prediabetes.
• However, the benefit must be weighed against potential weight gain, edema, and increased fracture risk. Lower doses may lessen these adverse effects.

What Autoimmune Conditions Should People with Type 1 Diabetes Be Screened For?

• Screen soon after diagnosis and periodically thereafter
• Autoimmune thyroid disease
• Other autoimmune conditions, if suggestive signs and symptoms are present

Autoimmune Conditions Associated With Type 1 Diabetes

• Autoimmune thyroid disease
• Celiac disease
• Autoimmune liver disease
• Collagen vascular diseases
• Pernicious anemia
• Primary adrenal insufficiency
• Myasthenia gravis

How Does Diabetes Affect Bone Health

• People with type 1 or type 2 diabetes have a higher fracture risk than those without diabetes and the risk escalates with longer diabetes duration and poor glycemic control.
• People with type 2 diabetes on TZD, insulin, or sulfonylurea have an even higher fracture risk.

Optimizing Bone Health in People With Diabetes

• Screening in older adults (>65 years of age) and high-risk young adults and with dual-energy X-ray absorptiometry every 2-3 years.
• Nutrition and activity by counseling on calcium and vitamin D, aerobic and weight-bearing physical activity and fall precautions.
• Pharmacotherapy by choosing glucose-lowering medications with safe profiles for bone health and low hypoglycemia risk to prevent falls and consider antiresorptive, osteo-anabolic agents for those with a T-score ≤-2.0 or previous fragility fractures.

Are People with Diabetes at Increased RIsk For Cancer

• Diabetes is associated with increased risk of cancers of the liver, pancreas, endometrium, colon/rectum, breast, and bladder.
• Nevertheless, cancer screening recommendations are the same for people with diabetes as for those without diabetes.

How Prevalent is Nonalcoholic Fatty Liver Disease (NAFLD, NASH)

• 70% of type 2 diabetics will have NAFLD (nonalcoholic fatty liver disease)
• Screen individuals at risk (central obesity, >50 years of age, high plasma aminotransferase levels) to identify risk of developing complications such as cirrhosis and hepatocellular carcinoma
• High-risk individuals should be screened with fibrosis-4 (FIB-4) index score, based on a person's age etc.
• Weight loss with intensive lifestyle therapy and/or metabolic surgery, if appropriate.

Prevalence

• Approximately 70% of people with type 2 diabetes have NAFLD.
• Screening Goals: To identify individuals at risk for complications from nonalcoholic steatohepatitis (NASH), such as cirrhosis and hepatocellular carcinoma.
• To prevent death from liver disease.

High-Risk Individuals

• People with central obesity and cardiometabolic risks or insulin resistance.
• Individuals >50 years of age
• Those with persistent high plasma aminotransferase levels (AST/ALT >30 units/L for >6 months)

Screening Tool

• Calculate the fibrosis-4 (FIB-4) index score, which is based on a person's age, ALT and AST levels, and platelet count
• Screen with the FIB-4 index even if liver enzymes are normal and a FIB-4 index calculation tool is available online.

Management

• Weight loss with intensive lifestyle therapy and/or metabolic surgery, as appropriate, is recommended.
• Pioglitazone and glucagon-like peptide 1 receptor agonists are the preferred agents for treatment of hyperglycemia in adults with type 2 diabetes and NASH, unless decompensated cirrhosis is present.
• People with type 2 diabetes and decompensated cirrhosis from NASH should be treated with insulin.
• Statin therapy is safe in the setting of NAFLD and use with caution and close monitoring in people with decompensated cirrhosis.

Components of the Comprehensive Diabetes Medical Evaluation at Initial, Follow-Up, and Annual Visits

• Includes diabetes history, family history, personal history of complications and common comorbidities, past medical and family history, behavioral factors, medications and vaccinations, technology use, social network, social life assessment, physical examination, and laboratory evaluation.

Diabetes History

• Characteristics at onset (e.g., age, symptoms)
• Review of previous treatment plans and response and assess frequency/cause/severity of past hospitalizations

Family History

• Family history of diabetes in a first-degree relative and autoimmune disorder

Personal History of Complications and Common Comorbidities

• Common comorbidities (e.g., obesity, OSA, NAFLD), high blood pressure or abnormal lipids, macrovascular and microvascular complications and hypoglycemia: awareness/frequency/causes/timing of episodes

Behavioral Factors

• Eating patterns and weight history and assess familiarity with carbohydrate counting
• Physical activity and sleep behaviors including screen for obstructive sleep apnea

Social Network

• Identify existing social supports and surrogate decision maker and advanced care plan
• Identify social determinants of health (e.g., food security, housing stability & homelessness, transportation access, financial security, community safety)

Physical Examination

• Height, weight, and BMI; growth/pubertal development in children and adolescents, blood pressure determination, thyroid palpation, and comprehensive foot examination
• Includes visual inspection, screen for PAD, determination of temperature, vibration or pinprick sensation, and 10-g monofilament exam

Laboratory Evaluation

• Includes A1C, lipid profile, liver function tests, spot urinary albumin-to-creatinine ratio, Serum creatinine, thyroid-stimulating hormone in people with type 1 diabetes, Vitamin B12 if on metformin, and Complete Blood Count.

Essential Tasks to Help People with Diabetes Achieve Their Health Goals

Including referral for diabetes self-management education and support (DSMES), referral for medical nutrition therapy (MNT), counsel on routine physical activity Counsel on and support cessation of tobacco products and vaping, counsel on health behaviors, and support and refer to behavioral health professionals for psychosocial care

DSMES

• Is critical for all people with diabetes
• Times to refer are annually, at diagnosis, when not meeting treatment goals, when complicating factors develop, and when transitions in life and care occur
• Include provide culturally appropriate content; be responsive to individual preferences, needs, and values and use positive, strength-based language that puts people first. Benefits can include improved diabetes knowledge, self-care, and quality of life.
• Lower A1C and self-reported weight reductions, reduced all-cause mortality risk, acute care and hospital services utilization, and lower health care costs. Proven outcomes increased use of primary care and preventive services and positive coping behavior

Psychosocial Care for All People with Diabetes

• Clinicians should implement psychosocial screening protocols, including for diabetes distress.
• Screened at least annually or when changes in disease, treatment, or life circumstances occur.
• Interventions should be collaborative, person-centered, and culturally informed and consider individuals' treatment burden.

Diabetes Distress

• The ongoing demands of diabetes self-care and the possibility or reality of disease progression are directly linked to reported diabetes distress.
• Significantly affect medication-taking behavior and linked to higher A1C, lower self-efficacy, and less-optimal eating and exercise behavior.

MNT

• There is no one-size-fits-all eating pattern
• Successful MNT programs are flexible, realistic, and sustainable
• Provided by registered dietitian nutritionist
• Offered to all with Type 1,2 diabetes, prediabetes and gestational diabetes mellitus

Key Nutrition Principles

• Include nonstarchy vegetables, whole grains, nuts and seeds and low-fat dairy products

Minimize

• Minimize meat, sugar-sweetened beverages, sweets and refined grains
• Data do not support a scientific distribution of macronutrients, people with diabetes may choose from a variety of healthy eating patterns.

Support Positive Health Behavior

• Motivational interviewing
• Patient activation
• Goal-setting and action-planning
• Identification of social support resources

Importance of 24-Hour Physical Behaviors for Type 2 Diabetes

• Activities may include sitting, stepping and SWEATING (MODERATE-TO-VIGOROUS ACTIVITY)
• SLEEP and Maintaining CHRONOTYPE/CONSISTENT TIMING

Sitting/Breaking Up Prolonged Sitting

• Limiting sitting and breaking it up (every 30 min) with short regular bouts of slow walking/simple resistance exercises can improve metabolism.

Stepping

• Involves only 500 steps/day and a five or six minute brisk walk per day leads to a greater life expectancy

SWEATING (Moderate-To-Vigorous Activity)

• Encouraged with ≥150 min/week or moderate with intensity supplemented by two to three resistance, flexibility, and/or balance sessions.
• As little as 30 min/wek of moderate-intensity physical activity improves the metabolic state

SLEEP Duration

• Should be consistent and uninterrupted, even on weekends impacting A1C
• Chronotype- evening chronotypes may be susceptible to physical inactivity and should be monitored.

Assessment of Glycemic Status

• A measurement
• Continuous glucose monitoring using appropriate

Considerations for Monitoring Glucose

• Monitor at initial visits, and ensure that treatment plans respond appropriately and are being followed.
• Consider factors relating to altered red blood cell turnover which may lead to potential interferences in the accuracy of a reading

Glucose Assessment Via CGM - Ambulatory Profile

• Ensure adequate data is available and review daily data to assess efficacy of management plans and solutions
• Identify potential hyperglycemic patterns and provide individuals with potential paths forward

Setting/Modifying Glycemic Goals

• Individualize based on key characteristics of the person with diabetes, and their preferences
• A1C 1.7,
• Preprandial: plasma 80-130 mg/dL
• Postprandial: 180 mg/dL
• Review individual responses in order to better address each patients underlying characteristics

Hypoglycemia Assessment, Prevention and Treatment

• Hypoglycemia is categorized according to severity levels,
• Level 1 glucose below 70mg/dL
• Level 2 glucose below 54 mg/dL
• Level 3 Is a severe event with altered mental and/physical states irrespective of glucose leves

Management of Hypoglycemia

• Check and review history in order to better asses moving forward and be hyper aware
• Promote CGM use in high-risk individuals, and ensure that glucagon is available for those taking insulin

Diabetes Technology

• Includes insulin pumps, connected insulin pens and pen caps, and CGM systems.
• Can include diabetes self-management software.

General Diabetes Technology Principles

• Offer to those with diabetes that are able-bodied.
• Also providing ongoing education

BGM

• Encourage those to check glucose based on appropriate assessment levels.

CGM

• Beneficial as an aid for those pregnant, as well as periodic management.
• Consider cost effectiveness.

Personal Diabetes Technology Use in the Hospital

• Manage and continue to administer treatment as appropriate or when clinically appropriate
• Follow any procedures and institutional guidelines
• Ensure that proper technology is being used and implemented
• Be supervised and safe.

BARIER BUSTER

• Actively schedule visits
• Involve and incorporate screenings
• Treat as appropriate and prescribed

To Address and Prevent inertia

• Conduct practice-based screenings for likely issues,
• Make team based approaches and provide assistance to patients.

IMROVE DECISION -MAKING

• Review treatment algorithms.
• Integrate technology.

Injections As Appropriate

• The key is appropriate timing and management
• Appropriate dosages.

Consider the Individuals Profile

• Review and adjust treatment plans according to circumstances relevant to the individuals background.
• Review how it is affecting their health.

This content covers scenarios for pioglitazone use in secondary cardiovascular prevention, medication choices for hyperglycemia in type 2 diabetes and NASH, and management of diabetes with decompensated cirrhosis. It also addresses diabetes treatment goals, interprofessional care teams, monitoring statin therapy in NAFLD, and the role of community partners.