Dealing with Type 1 Diabetes Mellitus

 

 In the last article “The Assessment, Criteria for High Blood Pressure: Its Conventional vs Non-Drug Approaches” here:

https://scientificlogic.blogspot.com/2023/

posted on Thursday, July 20, 2023, we mentioned two most common chronic lifestyle diseases, namely hypertension and diabetes. 

We have already briefly discussed high blood pressure, their outcome and management using conventional drug-based approaches as well as very briefly listed in point forms, a range of other alternative therapeutic approaches to deal with this problem.

We shall now briefly discuss diabetes mellitus, the next most common disorder in all countries, especially among affluent societies.

First of all, diabetes mellitus is entirely different from another diabetes called "diabetes insipidus" that is a rare endocrine disorder involving the posterior pituitary peptide hormone, the antidiuretic hormone (ADH). This causes the fluids in the body to become out of balance, causing large amounts of urine output resulting in extreme thirst.

Diabetes insipidus also is called arginine vasopressin deficiency and arginine vasopressin resistance. We shall not deal with this here as it is different from diabetes mellitus commonly called just diabetes. 

We shall also not deal with type 1 diabetes here that requires insulin injections. Briefly, Type 1 diabetes, also called insulin-dependent diabetes (IDDM) or juvenile diabetes, normally develops in children, teens, and young adults, but it can happen at any age especially after type 2 diabetes has lost all its ability to produce insulin. 

Type 1 diabetes is less common than type 2—about 5 - 10% of people with diabetes have type 1.

In diabetes type 1, the pancreas does not make insulin, due to an auto-immune response that attacks the islet cells in the pancreas that make insulin. 

This may be due to viruses, genes, dietary factors or chemical exposure that trigger autoimmune response. Type 1 diabetes may also arise from chronic pancreatitis, or the result of pancreatic surgery. 

As type 1 insulin-dependent diabetes is comparatively rarer, we shall not discuss this further.   

In diabetes type 2, the pancreas makes less insulin than used to, and your body becomes resistant to insulin. This means your body has insulin, but stops being able to use it.

Diabetes mellitus is a world-wide epidemic that shall become wider and afflicting most people especially among the Indians and Malays in Malaysia. 

It was found that individuals with type 2 diabetes mellitus (DM) globally were over 30 million in 1983, 171 million in 2000, 220 million in 2009 and 330 million in 2018, 380 million in 2021. 

The prevalence rate seems to double every few years. From 1998 to 2009 the prevalence rate rose to a frightening rate 239 % in Canada alone and has been projected to rise sharply within the next 10 years and shall continue to rise. The Centre for Disease Control (CDC) in the United States projected a 40 % increase of DM among Americans over their lifetime. 

The same scenario we can expect in this country due to our changing fare (dietary lifestyle).

Type 2 DM is the most common ailment that afflicts the developed and developing world. The rising trend is attributable to other factors too such as obesity, sedentary lifestyles, aging population and improved survival rates among diabetics.

Type 2 DM is also linked to high healthcare costs. Figures taken from other countries, for instance in a report “An Economic Tsunami: The Cost of Diabetes in Canada” from 2009 the estimated cost of type 2 DM in 2010 was US $ 12.2 billion and projected to surge to US $ 16.9 billion by 2010, perhaps to US $ 30 billion by the end of this year 2023. We may have similar trends in Malaysia although data is scant and not well-studied.

       

Our hope is that type 2 DM is highly preventable, especially to reduce the risk of other linked diseases such as cardiovascular mortality by at least 10 percent or more.

Pathophysiology:

 The pathophysiology of type 2 DM is multifaceted and complicated, essentially consisting of hyperglycemia and impaired insulin secretion.

 Carbohydrate consumption and its breakdown into glucose for absorption triggers the release of insulin by the beta cells from the pancreas. Insulin in turn triggers the uptake of glucose by the cells through the GLUT-4 glucose transporter. 

Insulin resistance (IR) may ensue after exposure to chronically high serum glucose levels. Patients on steroid therapy and physical inactivity may also face high risk of developing type 2 DM. 

Scientists are in the opinion that type 2 DM is amplified by the peripheral cells inability to efficiently uptake glucose in response to insulin, or insulin becomes ineffective due to the absence of a coenzyme called glucose tolerance factor (GFT) that requires chromium and niacin to assist when the beta islet cells dysfunction. 

Insulin role in exciting cellular glucose uptake decreasing hepatic gluconeogenesis, together with increasing adipose tissue triglyceride synthesis, together with glycogen regulation and vascular quality are crucial factors in impaired 2 DM. 

Diabetes is ironically labelled as “starving amidst the feast” whereas, insulin resistance (IR) indicates impaired glucose transport into muscle cells that explains for the “starving” amidst the hyperglycemia “feast”  

Furthermore, cellular starvation feedback mechanisms exacerbate hyperglycemia by exciting hepatic gluconeogenesis and fat breakdown.

IR also stimulates the production of free fatty acids and inflammatory cytokines.

Inflammatory markers shown to be elevated in DM comprise C-reactive proteins, II -6, plasminogen activator inhibitor -1 (PAI -1), and tumor necrosis factor (TNF)- alpha, in addition to white cell count.

Adiponectin is an anti-inflammatory cytokine that has been demonstrated to reduce plasma levels of free fatty acids. High adiponectin is associated with improved lipid profiles, glycemic control, and reduced inflammation.  DM has also been shown to be associated with a reduction in adiponectin.

Most of the studies on type 2 DM pathophysiology were earlier concentrated on IR. However, the role of the pancreas has increasingly been recognized.  Beta islet cells are well accepted to produce insulin. However, these are not the only pancreatic islet cells. Alpha islet cells produce glucagon, considered an equivalent of insulin. The interaction between insulin and glucagon is typically very tightly synchronized.

 The increased glucagon further exacerbates the hyperglycemia state in type 2 DM as a result of IR and impaired insulin secretion.

Genetics also influences the pathogenesis of type 2 DM. Medical genomics is a field of active medical research with high potential for us to understand DM further. Genomic single-nucleotide polymorphisms (SMPs) have been demonstrated to be linked with DM risk.  Environmental factors may also in turn increase genetic risk in DM as with all other diseases. 

For instance, exposure to arsenic in drinking water increases the risk of type 2 DM, and so is the Bisphenol A used in hard plastic and resins shown to be linked to DM. Pesticide exposures, especially the organophosphates and chlorinated pesticides may be associated with an increased risk of DM.

We shall later in a separate write-up look at the management of DM using conventional pharmaceuticals such as metformin and glucophage the main type of biguanide among other less commonly used such as alpha-glucosidase inhibitors, biguanides, bile acid sequestrants, dopamine-2 agonists, DPP-4 inhibitors (gliptins), meglitinides (glinides), SGLT2 inhibitors, sulfonylureas and thiazolidinediones.

We shall compare these agents with a more integrative approach such as lifestyle changes, smoking cessation, exercise, diet and nutrition such as using diets low in glycaemic index involving high fibre intake, dietary fat, mind-body therapy, cognitive-behavioural therapy, biofeedback, sleep medicine, an impressive long list of natural medicine such as using coccinia cordifolia, salacia reticulata, soya, gynostemma pentaphyllum, silymarin, citrullus colocynthis, cinnamon, fenugreek, bitter melon or bitter gourd (Momordica charantia).

In Malay native medicine, they use herbs and plants which in the Malay language are called, such plants as hempedu bumi, kalmegh, Andrographis paniculata, sambung nyawa, akar sebiak, gynura procumbens, ulam raja, pokok kenikir, dukung anak, pokok gajus, belimbing buluh, belimbing asam, pokok bunga raya, kembang sepatu,misai kucing, kumis kucin. 

They also include Helminthostachys zeylanica, a herbaceous fern found in southeastern Asia and Australia, commonly known as kamraj and tunjuk-langit in Malay. 

We shall try to include nutritional supplements as well using vitamin D, chromium together with niacin (GFT), omega-3 fatty acids, magnesium, antioxidants, vitamin E, L-carnitine, benfotiamine and discuss their pharmacognosy (mode of action) together with their risks.

Benfotiamine in postprandial endothelial dysfunction has been suggested as a link between metabolic syndrome and atherosclerosis. This state is linked with oxidative stress, hyperglycaemia, hypertriglyceridemia and altered nitric oxide function as well as glucose-protein complexes in foods, glycation end products (AGEs). 

These complexes are produced at high temperatures and activate AGE-specific receptors, which in turn activates monocytes and endothelial cells and causes inflammation.

 Benfotiamine is a synthetic analogue of thiamine (vitamin B1) with very high bioavailability. It activates transketolase, the enzyme that removes AGEs, and subsequently increases postprandial endothelial.

In a small study it was shown that 350 mg of benfotiamine after a meal completely eliminated vascular measurements of postprandial endothelial dysfunction in 13 patients with type 2 DM. 

In a separate study it was shown that benfotiamine improved microalbuminuria in diabetic patients.

We may also like to have a look at the use of hormones such as incretins, a hormone produced in the small intestines that enters the vasculature and triggers the release of insulin by the pancreatic beta cells. 

We may also look at two incretins, namely glucagon-like peptides (GLP-1) and the gastric inhibitory peptide (GIP).

Scientists have discovered another class of agents that inhibits dipeptidyl peptidase-4 (DDP-4), an enzyme that degrades GLP-1 and GIP.  They have demonstrated their efficacy in increasing insulin levels and decreasing glucagon.

 However, even to summarize them, let alone to discuss them is going to be exceedingly lengthy and time consuming as I have other interests too to spend my time, such as astrophysics, mathematics, forensic science and toxicology to write also other than spending my time writing on medicine or nutrition. 

Frankly, it would be more enjoyable for me to spend my time on my hobbies such as playing my violin and flute than to simplify technical papers and summarize them for lay, but my gentle readers. For this, I thank you for your patience.  

 

But we can give this a try if given time and space.