Diabetes Mellitus Evidence: Causes, Diet, Medications

What is diabetes mellitus?

Diabetes mellitus is a chronic condition in which the body cells do not take up sugar (glucose) from the blood efficiently, which results in increased blood glucose levels or hyperglycemia.

Types and Causes

In diabetes type 1, the pancreas does not produce enough of the hormone insulin, which results in a reduced uptake of glucose from the blood into the cells ^[18]. Diabetes 1 is considered an autoimmune disease in which antibodies attack the beta cells of the pancreas. The exact cause is not known but genetic predisposition and possibly some environmental factor, such as a viral infection and early introduction of solid foods in infants, may be involved ^[36]. Diabetes 1 commonly develops in adolescents and young adults but also after age 30 ^[18,43].

In diabetes type 2, the body cells develop resistance to insulin and therefore cannot efficiently take up glucose from the blood. Additionally, with the progression of the disease, the pancreas usually starts to produce less insulin ^[5]. Diabetes 2 usually develops in individuals older than 30 years of age, probably due to a combination of genetic predisposition ^[36], obesity, especially abdominal obesity ^[45,46], and physical inactivity ^[5,6,12], but can also appear in children and lean individuals ^[12,18]. Currently, there is no firm proof that diets high in sugar or carbohydrates or any other diet ^{[1,2,3,4,5,13]} or work-related psychological stress ^[44] increase the risk of diabetes 2.

Gestational diabetes appears for the first time during pregnancy and usually disappears spontaneously after delivery ^[18].

Diabetes can also occur in chronic pancreatitis ^[19], pancreatic cancer ^[20], autoimmune disorders, such as systemic lupus erythematosus ^[6], in Cushing syndrome ^[6] or as a side effect of drugs, such as corticosteroids (prednisone) ^[40], thiazide diuretics (diazoxide, hydrochlorothiazide) ^[39], atypical antipsychotics (clozapine, olanzapine and risperidone) ^[41] or, less likely, beta-blockers (propranolol) ^[42] and statins (lovastatin) ^[37,38].

Prediabetes means fasting glucose levels between 100 and 126 mg/dL, glucose levels in glucose tolerance test (OGTT) 140-200 mg/dL, and HbA1c levels between 5.7 and 6.5% ^[17]. Prediabetes does not necessary lead to diabetes ^[18].

Symptoms and Signs

When the blood glucose levels exceed 10 mmol/L, the excessive glucose starts to get excreted into the urine and can cause ^[18,30]:

Frequent and excessive urination
Excessive thirst (due to dehydration)
Hunger
Fatigue
Unintentional weight loss
In severe hyperglycemia: rapid breathing, fruity breath odor, flushed face and nausea

NOTE: A person with blood glucose levels below 10 mmol/L can be without any symptoms.

Complications

Untreated or poorly treated diabetes can, in long-term, result in complications ^[14,30]:

Frequent infections
Nausea and early satiety after eating due to slow movement of the food through the stomach (gastroparesis) or weakness and dizziness after meals due to rapid gastric emptying (dumping syndrome)
Severely increased blood glucose levels (hyperosmolar hyperglycemic nonketotic syndrome)
Accumulation of ketones in the blood resulting in increased blood acidity (diabetic ketoacidosis)
Diabetic foot ulcers
Blurred vision or blindness due to a damage of the eye retina (diabetic retinopathy) or lens
Numbness, tingling, itching or burning in the feet and hands due to a nerve damage (diabetic neuropathy)
Carpal tunnel syndrome with pain in the wrist and tingling in the thumb, index and middle finger ^[35]
Diabetic dyslipidemia (high LDL and low HDL cholesterol and high triglyceride levels), possibly leading to hardening of the arteries (atherosclerosis), coronary heart disease, heart attack or stroke ^[33,51,52]
High blood pressure
Chronic kidney disease (diabetic nephropathy)
Erectile dysfunction

Metabolic syndrome (high blood glucose + low HDL cholesterol + high triglycerides + abdominal obesity + high blood pressure) is a common complication in poorly treated diabetes type 2 and also type 1 ^[51,52].

Diagnosis

A doctor can make a diagnosis of diabetes mellitus from a combination of ^[17]:

Increased fasting blood glucose levels (>126 mg/dL)
Increased blood glucose levels after oral glucose tolerance test (OGTT) (>200 mg/dL)
Increased glycated hemoglobin (HbA1c) levels (>6.5%)
The presence of ketone bodies in the blood (in severe cases)
The presence of glucose in the urine (in severe cases)

Hemoglobin (HbA1c) reflect your recent average blood glucose levels; the blood HbA1c values above 7% indicate that your average blood glucose levels in the last 2-3 months have been increased ^[11]. Doctors recommend individuals with diabetes to test for HbA1c every 3 months and to maintain the levels below 7% ^[11].

Normal HbA1c levels for people without diabetes are 4-5.6% ^[11]. The levels between 5.7 and 6.4% indicate increased risk of diabetes and levels 6.5% or higher indicate diabetes ^[11].

Treatment

In diabetes type 1, insulin injections are usually required to maintain normal blood glucose levels ^[30].

In diabetes type 2, normal glucose levels can usually be controlled by diet, weight loss, exercise and oral glucose-lowering medications; in later stages, insulin is often needed ^[5].

In gestational diabetes mellitus, diet, oral medications and insulin injections can be used ^[25,26,27].

Diet

There seems to be no specific nutrient, supplement (omega-3 fatty acids, dietary fiber), food (nuts, legumes, dairy) or diet (low-glycemic index, low-carb, low-sugar, high-protein, vegetarian, Mediterranean) that would–in long-term–help to control blood glucose levels in individuals with diabetes type 2 ^{[3,4,5,9,10,12,13,23,47,50]}. Every diabetic needs to find out which foods raise his or her blood glucose and HbA1c levels.

Foods that can quickly and prominently raise blood glucose levels after the meals are said to have high glycemic index (GI); examples include white wheat products (bread, pasta, pancakes), cornflakes, instant oatmeal, white rice, potatoes and sugary foods and beverages (candies, dates, raisins, soda, fruit juices) ^[7]. There is no evidence that avoiding these foods in long-term results in lower blood glucose levels than any other diet ^[13,15,16].

Table sugar (sucrose) and other sugars do not raise blood glucose levels more than starch ^[50]. Sugar alcohols or polyols (isomalt, lactitol, maltitol, mannitol, sorbitol, xylitol) raise glucose levels less than sugars and non-nutritive sweeteners (acesulfame-K, aspartame, erythritol, neotame, saccharin, stevia, sucralose) do not raise it ^[50]. Fructose raises blood glucose levels less than sucrose, but large amounts (>20% of daily calories) should be avoided because they can raise total and LDL cholesterol ^[53] and triglycerides ^[54].

In women with gestational diabetes–according to one 2014 systematic review–low-glycemic index diet was associated with less insulin use and lower birth weight in the babies ^[27].

In order to maintain normal glucose and cholesterol levels and blood pressure, try to ^[12,47,50]:

Avoid high-calorie meals
Lose weight (if overweight); avoiding sweet foods, white wheat products and potatoes may decrease food craving
Limit intake of saturated fat (from red meat and cheese) to <7% of total daily calories
Avoid foods high in trans fat (French fries, cheeseburgers, chicken nuggets, doughnuts, crackers, chips Vanaspati ghee ^[34])
Limit intake of cholesterol (from organ meats and egg yolks) to 200 mg/day
Avoid high sodium intake

Exercise

According to the American College of Sports Medicine, the optimal amount of exercise that can improve insulin resistance in individuals with diabetes 2 is, for example, walking 150 min/week at 4 mph (6.4 km/h) or running 75 min/week at 6 mph (9.6 km/h) ^[48]. Resistance exercise that results in muscle mass gain can also reduce insulin resistance ^[48,49].

Oral Hypoglycemic Drugs

According to one recent review of studies that most effectively reduce HbA1c levels, help to maintain healthy body weight, reduce the risk of death from heart disease and are most safe are:

The Effectiveness of oral diabetes medications for adults with diabetes 2 ^[24]:

Metformin as a single medication most effectively reduces HbA1c.
Metformin is more effective in reducing HbA1c when used in combination with glitazones (pioglitazone), GLP-1 receptor agonists (exenatide), sulfonylureas (glipizide, glyburide) SGLT-2 inhibitors (dapagliflozin) or DPP-4 inhibitors (saxagliptin).
Metformin, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors were associated with reduced body weight.

Drugs that cause most side effects ^[24]:

Hypoglycemia: glipizide, glyburide and other sulfonylureas, metformin
Nausea, vomiting or diarrhea: metformin; exenatide and other GLP-1 agonists
Genital fungal infections: metformin in combination with an SGLT-2 inhibitor, such as dapagliflozin
Weight gain: glipizide, glyburide, pioglitazone

In gestational diabetes mellitus, glyburide and metformin have been shown to be effective and safe for the mother and the baby ^[25,26].

Insulin

The hormone insulin enables blood sugar to enter the body cells. Insulin is usually injected under the skin using a syringe and needle, insulin pen or insulin pump.

One brand of inhaled (powdered) rapid-acting insulin for use before meals was approved by the US Food and Drug Administration in 2014 ^[29]. Its effectiveness in reducing HbA1c levels is similar than injectable rapid-acting insulin in individuals with diabetes 1 and better than oral hypoglycemic drugs in those with diabetes 2 ^[29,31]. Its long-term safety is not yet known. It may not be covered by several health insurance plans. Diabetics who use it still need to use injections of long-term insulin ^[29]. Diabetics with lung disease (asthma or COPD), ketoacidosis or those who smoke should not use it ^[29].

Insulin side effects ^[32]:

Redness and swelling at the site of the injection
Blurry vision (at the onset of treatment)
Weight gain
A drop of blood glucose levels (hypoglycemia) with sudden onset of paleness, nervousness, weakness, sweating, impaired consciousness or, if not treated, death
Diarrhea
Generalized allergic reaction with skin itching, facial swelling (angioedema), difficulty breathing or, rarely, death

Prognosis

Diabetes type 1 is usually a life-long disease, which cannot be cured but can be treated ^[30].

Diabetes type 2 tends to be a progressive disease, but it can sometimes be cured completely or controlled just by diet ^[5].

Prevention

There seems to be no known prevention for diabetes type 1.

It can help you prevent diabetes type 2 if you maintain a healthy body weight ^[5,12].

It is not clear if diets with low glycemic index (GI) or glycemic load (GL) ^[13,16,21] or any other diet ^[18,23,22] decreases the risk of developing diabetes type 2.

References

Diabetes Mellitus