Type-2 Diabetes

Blood sugar disorders, such as type-2 diabetes, involve an imbalance of glucose in the bloodstream, which can include low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia and insulin resistance). Dysglycemia is a broad term that refers to such abnormalities in blood sugar stability. While both hypo-and hyperglycemia involve differing symptoms and mechanism, they both result in a decrease of glucose (sugar) in cells leading to impairment of cellular function. It is almost impossible for a person suffering from a chronic disease to recover or move towards homeostasis if the patient suffers from a chronic blood sugar disorder. Common symptoms of Dysglycemia include:

  • Fatigue
    • Afternoon or midday crash
    • Between meals or after meals
  • Insomnia
    • Inability to stay asleep
    • Inability to fall asleep
  • Mood swings
  • Anxiety
  • Depression
  • Hair thinning
  • Infertility and hormone imbalances
  • Impaired metabolism for weight loss or gain.

Insulin Resistance and Type 2 Diabetes

Insulin resistance is identified as an impaired biologic response to insulin stimulation of target tissues, primarily the liver, muscle, and adipose (fat) tissue. In a normal insulin-sensitive individual, insulin works effectively to manage glucose, so the pancreas secretes the proper amount of insulin to adequately clear glucose from the bloodstream. In a person with insulin resistance, insulin works ineffectively. The pancreas must secrete large amounts of insulin to push glucose into the cells resulting in a compensatory increase in insulin production and elevated blood levels or hyperinsulinemia. The consequences of insulin resistance can result in hyperglycemia (high blood sugar), hypertension (high blood pressure) , dyslipidemia (high cholesterol) and  elevated markers of inflammation. Progression of insulin resistance can lead to metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus.1

For well over half a century, the link between insulin resistance and type 2 diabetes has been recognized. Insulin resistance is not only the most powerful predictor of future development of type 2 diabetes, it is also a therapeutic target once hyperglycemia is present.2  Insulin resistance, impaired glucose tolerance, prediabetes, and type 2 diabetes mellitus type 2 are all part of a progressive continuum. The Dysglycemia-Based Chronic Disease (DBCD) model3 identifies four distinct, evidence-based disease stages along the type 2 diabetes spectrum. According to Jeffrey Mechanick, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and a past president of the American Association of Clinical Endocrinologists (AACE),  Type 2 diabetes is a disease that “migrates” from a state of normal blood sugar level (normoglycemia) with insulin resistance, to prediabetes, to type 2 diabetes that can be asymptomatic, to more severe forms of the disease. This model encourages the earliest intervention focusing on structured lifestyle change.4

Prevalence of Insulin Resistance and Type 2 Diabetes

Insulin resistance syndrome is very common, affecting about 24% of United States (US) adults older than 20 years.1  Worldwide, the prevalence of insulin resistance ranges from 15.5 to 46.5%, among adults.5 More than 84 million people ages 18 and older have prediabetes in the United States.6 According to the Centers for Disease Control (CDC) more than 37 million Americans have diabetes (about 1 in 10), and approximately 90-95% of them have type 2 diabetes.7 The global prevalence of Type 2 diabetes is 463 million (9.3%) and is projected to reach 578 million (10.2%) by 2030.8   

Over one quarter of people over the age of 65 years have diabetes, and one-half of older adults have prediabetes, and the number of older adults living with these conditions is expected to increase rapidly in the coming decades. People with diabetes have higher incidences of all cause dementia, Alzheimer disease, and vascular dementia than people with normal glucose tolerance.9

Dysglycemia and Insulin Resistance in Mood Disorders

Patients with type 2 diabetes mellitus are 2 to 3 times more likely to have depression than those without diabetes.10 In addition, 40% to 60% of people with depression exhibit blood sugar regulation disruptions that increase the risk for diabetes,11  and insulin resistance doubles the risk of major depressive disorder.12 Evidence suggests three pathophysiologic or molecular mechanisms that link brain insulin resistance with major depression: the brain’s reward system, the hypothalamic-pituitary-adrenal (HPA) stress axis, and gray matter volume in certain brain regions.13Insulin resistance is present in more than half of all bipolar patients and is associated with a chronic course of illness, lack of response to mood stabilizing treatment, cognitive impairment and poor functional outcomes. Insulin resistance may modify the course of bipolar disorder and promote neuroprogression, defined by a more severe form of illness and poor outcome.14

Dysglycemia and Insulin Resistance in Cognitive Disorders

The term “type 3 diabetes” has been used in health media and literature to refer to Alzheimer’s disease (AD), since the neurodegenerative disease is linked to insulin resistance.15 Both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are attributed to impaired insulin signaling, and insulin resistance mediates the dysregulation of bioenergetics and progress to AD.16 Over 80% of patients with AD have type II diabetes (T2DM) or abnormal serum glucose, suggesting that the pathogenic mechanisms of insulin resistance and AD likely overlap.17 It has been suggested that agents targeting insulin signaling including antioxidant nutraceuticals and dietary supplements show potential therapeutic activity against the pathogenesis of both disorders.18

Dysglycemia and Insulin Resistance in SARS-COV-2 and COVID

Research presented at the Alzheimer’s Association International Conference® (AAIC®) 2021 suggests COVID-19 is associated with long-term cognitive dysfunction and acceleration of Alzheimer’s disease pathology and symptoms. “These new data point to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimer’s symptoms,” according to Heather Snyder, Ph.D., Alzheimer’s Association Vice President of Medical and Scientific Relations.19

Many studies have now shown that key risk factors for SARS-CoV-2 infection, severity, and even death are modifiable and risk for severe disease can be reduced. Diabetes is a well-documented risk factor for severe COVID-19, however even in nondiabetic persons elevated pre-infection blood glucose is a risk factor. A 2021 study20 found an association between pre-infection fasting blood glucose (FBG) and the risk of severe COVID-19 among patients with and without a diagnosis of diabetes. In patients without diabetes, a FBG in the prediabetic range, from 100 to 125 mg/dL, was associated with a greater risk for severe COVID-19. The authors concluded that “elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics.” Hyperinsulinemia in patients with insulin resistance and diabetes can lead to increased SARS-CoV-2 viral load and an increased inflammatory response, leading to more severe forms of infection with increased mortality.21 A recent study22 that included more than 300 cases of COVID-19 suggests that type 2 diabetes may predict long COVID at the time of initial diagnosis.

Conventional Medical Approach

According to the National Institutes of Health6 researchers don’t fully understand what causes insulin resistance but they think excess weight and lack of physical activity are major factors. Lifestyle intervention represents the cornerstone of treatment for insulin resistance. Recommended dietary intervention include a combination of calorie restriction and reduction of high glycemic index carbohydrates. Physical activity improves both calorie expenditure and insulin sensitivity in muscle tissue.1

According to the American Diabetes Association, while it may not be possible to defeat insulin resistance entirely, there are ways to make the body’s cells more receptive to insulin. Getting active is probably the best way to combat insulin resistance. No medications are specifically approved by the FDA to treat insulin resistance however diabetes medications like metformin and thiazolidinediones, or TZDs, are insulin sensitizers that lower blood sugar, at least in part, by reducing insulin resistance. 23 Pharmacotherapy should be started at the time type 2 diabetes is diagnosed unless there are contraindications; for many patients this will be metformin monotherapy in combination with lifestyle modifications. Additional and/or alternative agents may be considered in special circumstances, such as in individuals with established or increased risk of cardiovascular or renal complications. Because type 2 diabetes is a progressive disease in many patients, maintenance of glycemic targets with monotherapy is often possible for only a few years, after which combination therapy is necessary. Traditional recommendations have been to use stepwise addition of medications to metformin to maintain A1C at target.24

Functional Health Approach

At  A Wiser Mind our focus is on using a functional health approach for supporting brain health, in particular cognitive and mood disorders. Both conditions are strongly associated with Dysglycemia and insulin resistance.  Insulin resistance involves complex and intertangled vicious cycles that involve a web of multiple immune, endocrine and nervous system dysfunctions associated with:

  • Environmental toxins;
  • Infections;
  • Gut bacteria disruption and increased intestinal permeability;
  • Mitochondria dysfunction; and
  • Inflammation, oxidative stress and immune dysfunction.25-42

Clinical strategies for supporting a patient with a blood sugar disorder is done on an individualized basis depending on the presenting pattern Dysglycemia. The necessary first step is to stabilize blood glucose and insulin starting with diet and lifestyle. For insulin resistance it is also necessary break the excessive blood insulin vicious cycle by:

  • Resolving any persistent inflammation;
  • Initiating exercise at a rate to avoid overtraining and inflammation and increase intensity and duration slowly over time;
  • Improve the gut microbiome and resolve any patterns of increased intestinal permeability (“leaky gut”); and
  • Emphasize removal of endocrine disrupting chemicals and optimize detoxification function.

Considered in the broadest sense, targets for this therapeutic lifestyle approach include the following major modifiable factors:

  • Food intake and nutritional status;
  • Digestive system dysfunction, infection and imbalanced gut bacteria;
  • Imbalance in immune cells that promote versus dampen inflammation;
  • Dysfunctional mitochondria, the “power plants” in every cell responsible for manufacturing ATP (the body’s energy compound);
  • Psycho-emotional and physical stressors;
  • Hormonal imbalances; and
  • Exposure to and accumulation of toxins and dysfunction in the body’s detoxification system.
References and Citations

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