Functional Nutrition for Type 1 Diabetes

What is type 1 diabetes (T1DM)?

T1DM is an autoimmune disease in which the immune system attacks and destroys insulin-producing beta cells of the pancreas, resulting in insulin deficiency (1).

An estimated 1.24 million people in the US have type 1 diabetes (2).

Typically develops during childhood but sometimes presents in adulthood (2).

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What causes type 1 diabetes?

The exact cause is unclear and likely varies from person to person (1).

Genetics play a large role. Certain variants of the HLA-DQB1 and HLA-DRB1 genes are present it up to 90% of people with type 1 diabetes (3, 4, 5).

Environmental triggers may lead to the development of type 1 diabetes in susceptible individuals.

Potential triggers include (those with the strongest evidence are bolded) (6):

• Altered gut bacteria (7, 8)
• Certain viral infections (9, 10, 11)
• Certain bacterial infections (12)
• Early exposure to gluten (13, 14, 15)
• Early exposure to cow’s milk (16, 17)
• Exposure to chemical toxins (6)
• High birth weight or rapid weight gain (18, 19, 20, 21)
• Increased intestinal permeability (leaky gut) (22, 23, 24, 25)
• Psychological stress (26, 27)
• Vitamin D deficiency (28, 29)

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What are the symptoms of type 1 diabetes?

The classic triad is (2):

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

Other symptoms include (2):

• Blurred vision
• Electrolyte abnormalities
• Fatigue
• Muscle wasting
• Weakness

If it remains undiagnosed or untreated, T1DM can result in diabetic ketoacidosis (DKA), which can be life-threatening (30).

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What are common complications of type 1 diabetes?

1. Diabetic Ketoacidosis (DKA)

DKA occurs when…

• Blood sugar levels become high due to lack of insulin (the sugar can’t get into the cells to be used as fuel)
• Instead, the body must use fatty acids as a fuel source (31)
• Large amounts of ketone bodies are produced from fatty acids to be used as an alternative fuel source (31).
• Rapid accumulation of ketones makes the blood acidic and leads to metabolic acidosis (blood pH <7.35) (31).
• At the same time, hyperglycemia (BG >250 mg/dL) increases urination, resulting in dehydration and electrolyte imbalances (32).

Symptoms of hyperglycemia are usually present, as well as other symptoms such as abdominal pain, difficulty breathing, and altered mental status (30, 31).

Treatment involves administering insulin and fluids and monitoring glucose and electrolytes (31).

If left untreated, DKA can lead to respiratory failure, coma, and death (30).

2. Hypoglycemia

Hypoglycemia (blood glucose levels <70 mg/dL) causes shakiness, irritability, confusion, rapid heart rate, and hunger (33).

Could be caused by (34):

• Incorrect insulin administration
• Insufficient carbohydrate intake
• Increased utilization of carbohydrates (such as during exercise)

If left untreated, severe hypoglycemia can result in loss of consciousness, seizure, coma, and even death (33).

3. Neuropathy

High levels of glucose in the blood can damage nerves and cause numbness or weakness, known as neuropathy (35).

4. Infections

Patients with diabetes are at a greater risk of infection due to reduced immune functioning (36).

5. Retinopathy

Small blood vessels in the retina are highly susceptible to damage caused by high blood sugar levels. Over time, this causes retinopathy (damage to the retina) and progressive vision loss (37).

6. Nephropathy

High blood glucose levels damage nephrons in the kidneys and inhibit their ability to filter blood (38).

Eventually, if the nephrons are severely damaged, chronic kidney disease and end-stage renal failure can occur (38).

7. Cardiovascular disease

Patients with diabetes are at a higher risk for cardiovascular disease and tend to experience CVD events, such as heart attacks, earlier in life (39, 40).

Factors that contribute include hyperglycemia, dyslipidemia, and hypertension (39).

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How is type 1 diabetes diagnosed?

Criteria for the diagnosis of diabetes (41):

• Fasting plasma glucose (FPG) of 126 mg/dL or greater.
• OR 2-hour plasma glucose (PG) of 200 mg/dL or greater during an oral glucose tolerance test (OGTT) using a 75-gram glucose load
• OR A1c of 6.5% or greater
• OR in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose >/=200 mg/dL

The ADA recommends using plasma blood glucose rather than A1c to diagnose the acute onset of type 1 diabetes in patients with hyperglycemia symptoms (41).

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Are there ways to estimate the risk of developing T1DM?

Yes! You can measure antibodies to estimate the risk of developing T1DM over the next 5 to 10 years.

The most commonly measured antibodies include:

• Glutamic acid decarboxylase 65 (GAD65)
• Islet antigen 2 (IA-2A)
• Insulin (IAA)
• Zinc transporter 8 (ZnT8A)

Testing positive for 2 or more of these antibodies is associated with anywhere from a 27% to 70% chance of developing T1DM in the next 5 to 10 years (145, 146).

Additionally, T1DM, celiac disease, and thyroid antibodies often co-occur, so the ADA recommends screening for celiac disease and measuring TSH and thyroid antibodies at the time of T1DM diagnosis (147).

Cyrex array 5 measures a wide variety of predictive autoimmune antibodies, including those for T1DM.

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What are the recommendations for blood glucose monitoring?

1. Plasma glucose:

How often to test (42):

• Prior to meals and snacks
• At bedtime
• Occasionally postprandially
• Prior to exercise
• When hypoglycemia is suspected
• After treating hypoglycemia, until normal levels are achieved
• Prior to critical tasks (driving, etc.)

Treatment goals for most patients (33):

• Preprandial (before a meal) plasma glucose: 80-120 mg/dL
• Postprandial (1-2 hours after beginning a meal) plasma glucose: <180 mg/dL

Treatment goals for pregnant women (43):

• Fasting: <95 mg/dL
• One-hour postprandial: <140 mg/dL
• Two-hour postprandial: <120 mg/dL

Treatment goals for hospitalized patients (44):

• For the majority of critically ill and noncritically ill patients: 140-180 mg/dL
• For selected patients not at risk for significant hypoglycemia: 110-140 mg/dL

2. Hemoglobin A1c

How often to test (33):

• At least twice a year if the patient is meeting treatment goals
• Quarterly if the patient’s therapy is not meeting treatment goals or has recently changed therapy

Treatment goals for adults (33):

• For most nonpregnant adults: <7%
• For patients without hypoglycemia, who have a long life expectancy and no significant complications: <6.5%
• For patients with a history of severe hypoglycemia, limited life expectancy, long-standing diabetes, or advanced complications: <8%

Treatment goals for pregnant women (43):

• If it can be achieved without significant hypoglycemia: <6%
• If necessary to prevent hypoglycemia: <7%

Treatment goals for older adults (>65 years) (45):

• If the patient is otherwise healthy: <7.5%
• If the patient has multiple coexisting illnesses: <8-8.5%

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What medications or treatments are prescribed?

1. Insulin

Insulin treatment is essential to prevent hyperglycemia and DKA.

There are four types of insulin (46):

• Rapid-acting:
  • Starts working in 15-30 minutes
  • Lasts for 4-5 hours
  • Taken before a meal to cover elevations in blood glucose from food
• Short-acting:
  • Starts working in 30-60 minutes
  • Lasts for 6-8 hours
  • Taken before a meal to cover elevations in blood glucose from food
• Intermediate-acting:
  • Starts working in 1-2 hours
  • Lasts up to 10-16 hours
  • Taken once or twice a day to lower blood glucose levels when rapid- or short-acting insulins stop working
• Long-acting
  • Starts working in 2 hours
  • Lasts up to 36 hours
  • Taken once or twice a day to lower blood glucose levels when rapid- or short-acting insulins stop working

The ADA recommends using rapid-acting insulin to reduce hypoglycemia risk (47).

Insulin needs can be estimated and dosed based on weight, meal composition, and energy requirements (47).

2. Pramlintide

Pramlintide is the synthetic form of amylin, a hormone normally secreted with insulin that helps regulate glucose metabolism (48).

It is sometimes added to insulin or used as a separate injection in order to improve glycemic control (49, 50).

3. Artificial pancreas

The artificial pancreas, also called a “closed-loop system”, combines a continuous glucose monitor (CGM) with an insulin pump to mimic the functions of the pancreas (51, 52).

4. Pancreas or islet cell transplantation

Transplantation is usually reserved for patients who have recurrent ketoacidosis or severe hypoglycemia, or for those who have had a kidney transplant (47).

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What diets are best for type 1 diabetes?

1. Carb Counting

There is some evidence that carb counting is more effective than other insulin dosing methods, but more research is needed (54, 55).

2. Low-glycemic diet

In children with type 1 diabetes, a low-glycemic diet significantly lowers HbA1c levels and reduces hyperglycemia without increasing the number of hypoglycemic episodes (56, 57, 58).

3. Dietary Approaches to Stop Hypertension (DASH) diet

In adolescents with type 1 diabetes, adherence to the DASH diet lowers A1c levels, improves blood lipids, and reduces blood pressure (59, 60, 61).

4. Low-carbohydrate (<130 grams) diet

Although the evidence is mixed, some studies suggest that low-carbohydrate diets reduce HbA1c and insulin use (62, 63, 64).

5. Ketogenic diet

Preliminary research suggests that a ketogenic diet containing 30-55 grams of carbohydrates per day may reduce HbA1c and improve glycemic variability in adults with type 1 diabetes (65, 66).

Potential concerns:

• May increase the risk of hypoglycemic episodes (65).
• Reports of decreased growth and dyslipidemia in children (67).
• Not recommended for women who are pregnant or lactating or people who are at risk for disordered eating (53).
• Diet-induced ketoacidosis in rare cases, usually w. comorbid illness or underlying conditions (68, 69)

6. Fasting-mimicking diet (FMD)

The FMD is a type of intermittent fasting that requires following a low-calorie, low-protein, high-fat diet for 5 days, then resuming normal eating for the rest of the month (70, 71).

One recent study found that a 4-day fasting mimicking diet (FMD) promoted pancreatic beta cell regeneration by turning on prenatal genes in mice with late-stage type 1 diabetes (72).

A 5-day boxed meal kit designed for fasting mimicking can be purchased from Prolon.

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How should hypoglycemia be treated?

Follow the 15/15 rule (73):

1. Eat or drink 15 grams of carbohydrates from one of the options discussed below, then wait 15 minutes.
2. Check blood glucose level. If still below 70 mg/dL, repeat steps 1 & 2.
3. Once SMBG returns to normal, consume a meal or snack to prevent recurrence of hypoglycemia.

Pure glucose (available in tablet or gel form) is the preferred treatment, but any carbohydrate-containing food will work (33).

Popular options that equal 15 grams of carbohydrates:

• Glucose tablets (3)
• Glucose gel (1 pouch)
• Honey (1 tablespoon)
• Jelly (1 tablespoon)
• Juice (4 ounces)
• Regular soda (5-6 ounces)

Foods containing fat or protein should be avoided, as these can slow carbohydrate absorption (33).

If the patient is unwilling or unable to consume carbohydrates by mouth, a glucagon injection can be administered to restore blood glucose levels (33, 74).

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What nutrients may be beneficial for T1DM?

1. Alpha-lipoic acid (ALA)

ALA is an antioxidant synthesized by the body, and it also participates in glucose homeostasis by protecting beta cells and enhancing glucose uptake (75).

Evidence from RCTs suggests that ALA supplementation (doses ranging from 300-1200 mg/day) may reduce oxidative stress, improve glycemic control, and reduce symptoms of neuropathy in patients with diabetes (76, 77, 78, 79).

2. Biotin

There is evidence that biotin supplementation (40 mcg/kg/day) for 3 months significantly lowers HbA1c in patients with type 1 diabetes when used in addition to insulin (80, 81).

3. Chromium

Currently there is no research on the effects of chromium supplementation in type 1 diabetes; however, lower chromium levels have been linked with higher HbA1c in these patients (82).

Chromium does appear to play a role in insulin sensitivity and carbohydrate metabolism, but the evidence regarding supplementation for the improvement of glycemic control is conflicting (83, 84, 85, 86, 87, 88, 89).

More research that properly measures chromium status is needed before any conclusions can be made (83).

4. Nicotinamide

Supplementation with nicotinamide (the active form of vitamin B3) in doses ranging from 1-50 mg/kg/day lowers insulin requirements by preserving residual beta cell function in patients with type 1 diabetes (90, 91, 92, 93).

5. Vitamin D

Low levels of vitamin D may increase the risk of developing type 1 diabetes, possibly due to its role in beta cell and immune functioning (94).

Preliminary research suggests that vitamin D supplementation (2,000 IU/day) in early childhood may protect against the development of type 1 diabetes (28, 29).

Evidence suggests that vitamin D supplementation (4,000 IU/day or 50,000 IU biweekly) improves glycemic control in patients with type 1 diabetes who also have low vitamin D levels (<30 ng/mL 25-OHD) (95, 96, 97).

6. Vitamin E

Although evidence does not support a role for vitamin E supplementation in glycemic control, several studies have found that supplementation with 750 IU/day of vitamin E may reduce the risk of diabetic complications by combating oxidative stress (98, 99, 100, 101).

7. Magnesium

Low magnesium levels are associated with poor glycemic control in children and adolescents with type 1 diabetes (102).

This occurs because a lack of magnesium impairs glucose-induced insulin secretion by beta cells (102).

Supplementation with magnesium (250-300 mg/day) reduces HbA1c and improves blood lipids in patients with diabetes (103, 104, 105).

8. Zinc

Zinc imitates the actions of insulin by increasing lipogenesis and glucose uptake in adipocytes and is also involved in the insulin signaling pathway (106, 107).

Lower plasma zinc levels are associated with poor glycemic control in patients with type 2 diabetes (108).

Evidence suggests that zinc supplementation improves glycemic control in patients with diabetes; however, more research is needed to determine adequate dosing and duration of treatment (109, 110, 111, 112).

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Do any other supplements improve glycemic control?

1. Curcumin

Evidence from animal and in vitro studies suggests that curcumin may prevent or delay the development of type 1 diabetes by reducing oxidative stress and protecting against beta cell death (113, 114).

Research in humans is conflicting, and studies have mostly been performed in healthy subjects or patients with type 2 diabetes (115, 116, 117, 118).

2. Fenugreek

One study found that supplementation with 100 grams of fenugreek seed powder per day significantly reduced fasting blood glucose and blood lipids (119).

3. Vinegar

In both healthy subjects and patients with diabetes, the addition of at least 2 teaspoons of vinegar to a meal containing complex carbohydrates reduces postprandial glucose levels by 20% (120, 121, 122).

The exact mechanism by which vinegar reduces blood glucose is unknown, but it may work by delaying gastric emptying (123, 124).

There is some conflicting evidence, so more research is needed (125, 126).

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What other lifestyle changes are recommended?

1. Get enough sleep

Sleeping less than 6.5 hours per night has been linked with poor glycemic control (higher hemoglobin A1c) in adult patients with type 1 diabetes (127, 128, 129).

2. Exercise regularly

Physical activity is associated with improved glycemic control, decreased inflammation, and reduced complications in type 1 diabetes (130, 131, 132, 133).

Exercise-induced hypoglycemia can be prevented by regularly monitoring blood glucose, reducing insulin, and consuming supplemental carbohydrates (134).

There is also evidence that adding short bursts of high-intensity, sprint-type exercise to aerobic exercise minimizes the risk for hypoglycemia (135).

The ADA recommends that adults with diabetes get at least 150 minutes per week of moderate-to-vigorous intensity aerobic activity (53).

4. Manage stress

Stress significantly increases serum glucose levels in the postprandial period in patients with diabetes (136, 137, 138).

Evidence suggests that mindfulness-based stress reduction techniques effectively reduce stress and are associated with improved glycemic control (139, 140).

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Are there any special considerations with pregnancy?

Women with type 1 diabetes have an increased risk for hypoglycemia during the first trimester, and many find it more difficult to recognize the signs of hypoglycemia (43).

Immediately following delivery, insulin sensitivity is increased, so there may be a decreased requirement for insulin during this time (43).

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What about type 1.5 diabetes?

About 10% of people with diabetes are classified as type 1.5, also known as latent autoimmune diabetes in adults (LADA) (141).

While classic T1DM develops in childhood, LADA is an autoimmune form of diabetes that develops in adults.

Some researchers consider LADA to be a subtype of type 1 diabetes, because it has a similar pathogenesis, which involves the autoimmune destruction of beta cells (142, 143).

The disease progression is slower than type 1 diabetes, and many patients don’t require insulin for the first 6 months (142).

These patients are often misdiagnosed with type 2 diabetes (144).