Part 43: Type 2 Diabetes is an Important disease: Expanding Medication Markets by Changing Treatment Criteria and Lowering Diagnostic Cut-off levels

Previous article described few examples of fundamental steps taken by industrialized nations over the past three decades on expanding medication markets. One example is the lowering laboratory cut-off values related to disease diagnosis criteria that led to massive increase of the number of otherwise healthy people with ‘diseases’, expanding global markets.  Type 2 diabetes (T2D) is used below as an example to illustrate this conflicting issue.

Type 2 diabetes:

Type 2 diabetes is a major public health and socioeconomic concern worldwide and is increasing in parallel with the obesity epidemic.  It is potentially a reversible metabolic condition secondary to excess accumulation of fat in key internal organs, such as liver, muscle, and pancreas, which occurs gradually over several years.  A significant reduction of this ectopic fat through dietary interventions (hypocaloric diet in conjunction with physical activities) or via bariatric surgery could lead to normalization of the fasting plasma glucose level rapidly. These speedy changes associated with blood glucose are primarily attributable to a significant reduction of hepatic fat, resulting in the normalization of hepatic insulin sensitivity and improved liver functions.

Once established, diabetes is a progressive disease:

The progression of T2D primarily due to insulin resistance and progressive pancreatic β-cell dysfunction.  Insulin resistance in muscle is one of the earliest identifiable abnormalities in T2D. Compared to the medication-driven control of blood sugar concentration which does not reduce the decline of β-cells or their functions.  Medications are designed to mostly control the blood sugar (and triglyceride) concentrations and hence, the reduction of a marker of longer-term glucose control, HbA1c level.  Despite speculations, current anti-diabetes medications have little effect on β-cell preservation.  Whereas, the reduction of insulin resistance, lifestyle-based loss of body weight though losing body fat. Consequently, subduing oxidative stress and inflammation, preventing deterioration of pancreatic functions in those with T2D.

The above is exemplified by the fact that despite excellent glucose control with antidiabetic agents, more than 50% of individuals with T2D will require insulin therapy within 10 years of starting treatment. This is in part because none of the currently marketed anti-diabetic agents have a tangible capability to modify or eliminate the root cause of T2D: the reversal of intra-organ fat, especially in the liver and protecting cells.  Thus, the current marketed antidiabetic drugs do not cure T2D nor stop the disease progression; requiring taking additional perhaps lifelong medications, including insulin.

Insulin resistance is not the only cause of the progression of T2D. Moreover, many factors affect insulin resistance, including oxidative stress and inflammation; collectively these lead to the progression of diabetes.  Other factors that cause the progression of T2D include, glucotoxicity and lipotoxicity, antibody formation against β-cells/ pancreatic islets cells, genetic susceptibility and generic abnormalities such as abnormalities of receptors and/or glucose transporter system, amyloid deposition in the islets, and resultant β-cell dysfunction, chronic inflammation and oxidative stress, negative effects of excess fatty acid, and inefficient incretin effect.

Current diabetes treatments are not yet capable of modifying root causes of T2D:

The advanced diabetes treatment options available today, including the use of multiple insulin regimens, continuous glucose monitoring, and use of an artificial pancreas, etc., still do not address the underlying root causes of T2D.  Although the currently available large armamentarium of anti-diabetic medications is effective in controlling blood sugar and HbA1c levels, these medications are designed primarily to control blood sugar and the reduce the severity of the disease.  Moreover, better control of diabetes reduces microvascular complication of diabetes, such as diabetic eye and renal disease and peripheral vascular disease, such has little effect on diabetes-associated macrovascular diseases, such as strokes and heart attacks (myocardial infarctions).

However, as with other organ failure-based diseases, such as chronic kidney disease and Alzheimer’s disease, the real treatment for T2D must be directed to reversing the underlying root cause: the removal of ectopic fat deposited in key organs.  In the absence of this (as we practice now), even in the presence of well-controlled glucose levels, the β-cells destruction and the disease progression will continue.  As with many other chronic diseases, prevention is the cure for diabetes; however, it seems that lately, prevention of diseases has been forgotten.

T2D prevalence rates are escalating at a higher rate in developing countries in Asia.  In contrast to industrialized western countries, where T2D occurs in parallel with obesity as determined by the body mass index (BMI), percentage rates of obesity as measured by the BMI are low in Asia (i.e., in fact, most Asian persons with T2D, BMI is within the ethnic specific normal range), yet the rate of T2D is increasing.  Currently, in Asian countries, the prevalence of obesity in adults ranges between 10% and 15%, but the prevalence of T2D is much higher.

Cause for discrepancy of incidences—BMI and progress of T2D in different continents:

Because both genetic and environmental factors contribute to T2D progression, it has been proposed that with increasing globalization, persons with Asian ethnicities have been unable to adapt to the food, environment, and lifestyles of westernized culture.  However, these studies continue to ignore the effects of mind‒body interactions, effects of chronic stress, cultural, employment and socioeconomic shocks (changes), and the associated chronic sustained stress that likely to exacerbates most chronic diseases, such as T2D, chronic kidney disease, mental disorders such as depression and other stress-related disorders, especially among immigrant populations.

Others have argued that Asians in particular, have a tendency (or genetic susceptibility) toward ectopic fat accumulation which increase the risks for T2D, and have speculated that downstream unidentified mechanisms cause fat storage.  If this is the root cause for T2D in persons of Asian origin with T2D, with higher abdominal circumferences (easily identify by measuring abdominal circumference—normal body size, including BMI but with large abdomens), shouldn't this be addressed? If this is the case, then the use of current anti-glycemic and anti-lipid meditations would not expect to have beneficial effects on this population; yet selling meditations to this population is a multi-billion-dollar market.

The lack of addressing the root-causes in chronic diseases is a major concern:

The mentioned fat infiltration of major organs in those with T2D, alters intracellular physiological controls.  For example, fatty infiltration of the liver results, in addition to non-alcoholic steatohepatitis (NASH), hepatic insulin resistance, suppression of gluco-neogenesis, and thus increased blood glucose levels.  Consequently, to maintain glucose homeostasis requires increased secretion of insulin from β-cells, leading to hyperinsulinemia (excess insulin in the blood), which diverts glucose into fat cells, making the obesity worse.

The approach of lowering the upper limits of fasting blood glucose from 120 to 100 mg/dL, seemingly overnight, approximately 25-years ago, led to an additional 75 million persons being diagnosed (labelled) with diabetes, worldwide.  Consequently, it forced millions of people to take otherwise unnecessary medications and subjected to frequent blood testing and adverse effects from medications.  New advances have been a made over the past few years, including the development of continuous glucose monitoring and the use of artificial pancreas, etc.  These technologies are needed and very useful, when used appropriately in patients requiring such tools for monitoring and treatment.

Negative effects of neglecting lifestyle changes:

The combination of hyperinsulinemia and fatty infiltration of the liver and pancreas, worsen pancreatic β-cell dysfunctions and impair insulin secretion.  The resulting insulin resistance, reduced insulin secretion, and elevated blood glucose, suppress the glucose uptake by skeletal muscles, exacerbating insulin resistance.  These negative vicious cycles can be most effectively intervened by affirmative changes in lifestyle.

Profit-driven medical propaganda by the healthcare industry has forced millions of people to spend countless amounts of money on unnecessary medications, including the so-called wonder drugs—statins.  Implementing appropriate lifestyle changes, especially, increasing regular physical activity and consuming less calories, are effective when properly implemented. Thus, these must be essential parts of clinical management of persons with T2D and obesity and is highly cost-effective.

Lifestyle changes, including restricting total caloric intake and increasing physical activities, living a healthier life, having less stress, and living in a less environmental polluted areas, etc., have a major impact on risk reduction for most chronic diseases, including T2D, obesity, metabolic syndrome, osteoarthritis, osteoporosis, and even Alzheimer’s disease.  Moreover, appropriate and effective lifestyle changes reduce the needs for surgical procedures, such as gastric bypass surgery (bariatrics), replacement of weight-bearing joints, liposuction, and other surgical procedures, such as coronary stenting, and cardiac bypass surgery, etc. Thus, lifestyle changes, not drugs, are the most important interventional factor in combating chronic disorders.

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Professor Sunil J. Wimalawansa, MD, PhD, MBA, DSc, is a physician-scientist, educator, social entrepreneur, and process consultant. He is a philanthropist with experience in long-term strategic planning, and cost-effective investment and interventions globally for preventing non-communicable diseases [recent charitable work]. The author has no conflicts of interest and received no funding for this work.