Since being diagnosed with Type 2 Diabetes in November 2000, I've been asking myself quite a few questions. What causes diabetes? What is the best treatment method? What is the best medication to use? What is the best diet to follow? What is the best exercise? Should I use supplements and if so which ones? Why hasn't a cure been found?

The most frequent answers I've been given can be summarized as take your pills, eat less, exercise more, use your meter more, and do whatever works for you! I'm currently in the process of discovering what works for me. See topical index for my discoveries to date. Also see Reference Links and Diabetes Books & Articles.

Purpose and topics

The search for the cause of diabetes has being going on for a long time and many research projects are currently underway. The fruits of all this research seems to be better ways to control and treat the symptoms of diabetes rather than a cure for it. Could research results be interpreted differently? Could such interpretation lead to a cure? What do I need to learn to interpret results? It is my intent to explore current research results and to document my findings. My focus will be on learning what offers the best chance of leading to a cure and, at the very least, to learn what may work best in the treatment of diabetes. Initially, my explorations are documented in a free-form style under a series of unconnected topic headings.

• Glutathione
• Glucokinase
• Glycolysis

Glutathione

My interest in Glutathione was triggered when I received an email in early September 2001 from someone who had read my story at http://diabetestype2.ca/. The email suggested a connection between Paxil and the onset of diabetes. I decided to investigate further and posted a message on the misc.health.diabetes newsgroup asking if anyone was aware of a connection between Paxil and diabetes. This query led to the exchange of a series of newsgroup postings that didn't lead, as is often the case within the newsgroup (where some see me as a person on the fringe, a spammer, and someone who likes spam) to any useful data but which did enable me to clarify my own thoughts.

Based on my personal experience, I also believe that there is a connection between taking Paxil and the onset of Type 2 Diabetes. Now I'm looking for the evidence. For example, I was diagnosed within 6 months of starting Paxil and my HbA1c indicated that I had high blood glucose levels for at least 3 months earlier. A year earlier my HbA1c was fine. So the indications in my case are that the onset of Type 2 Diabetes was within 3 months of starting Paxil! Coincidence? Maybe! At the very least, coincidence or not, more investigation is warranted. Also note that I can also personally attest that the withdrawal symptoms from Paxil are very severe. I plan to stop taking Paxil following the protocol advocated (which involve increasing my glutathione levels), I'm seeing my doctor on September 10 to talk about what I'm planning, to initiate a glutathione level test, and to get her advice. To date, January 2002, I haven't been able to find anyone who can conduct a glutathione test; none of the local labs have even heard of it! I'm in the process of identifying an endocrinologist working in a hospital (who could conduct a glutathione test) with research interests that I'm also interested in. At present, I've identified three possibilities working at the Ottawa Civic Hospital.

The Paxil prescribing information sheet (see page 4 and the lines I've highlighted in red: "reported adverse events" "rare events are those occurring in fewer than 1/1000 patients" and "Endocrine System: rare: diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis") indicates that a possible endocrine side effect of Paxil is Type 2 Diabetes! When I mentioned this to my doctor on September 10, she was unaware that the Paxil prescribing information sheet even mentioned diabetes! She immediately contacted the Paxil manufacturer's representative for clarification and received a letter (see page1 and page2) from the manufacturer the following day! I was surprised at the fast response! And this immediately piqued my interest further. The letter does not address why the Paxil prescribing information sheet indicates that diabetes is a possible side effect, but rather seeks to show that there is no connection. So why is diabetes shown as a possible side effect? What is the source of the data that led the manufacturer to state that there was a connection? I would like to see the data that led the manufacturer to conclude that there was a negligible chance (less than 1 in 1000 "rare event") that Paxil might affect the endocrine system and cause diabetes. I've started collecting experiences of people who, like me, are seeing an adverse relationship between Paxil and diabetes. Also of interest is the link being made by Dr Ana Sawka at the Mayo Clinic between Paxil and its effect upon blood glucose levels.

How could Paxil affect the endoctrine system and lead to Type 2 Diabetes? Based on what I've read so far, I'm leaning towards the idea that Paxil reduces the level of glutathione (GSH) in body cells and that this may contribute to, or even cause, Type 2 Diabetes. I suspect that this may only be the case for people already at a high risk of contracting Type 2 Diabetes. What percentage of the North American population are in the high-risk category? Is it less than 1 in 1000? Probably significantly higher! For more information on the side-effects of Paxil I'm currently reading Prozac Backlash by Joseph Glenmullen, MD and Beyond Prozac by Michael Norden, MD.

There is evidence that in order to minimize the withdrawal symptoms associated with stopping Paxil that the body's GSH levels have to be increased with the use of a Whey protein product; for example, Immunocal/HMS90 (which is rather expensive). Could the continued use of a Whey protein make it easier to control blood glucose levels? I'm continuing my research and am currently reading Breakthrough in Cell-Defense by Dr. Bounous and Dr. Somersall; Glutathione: Your Body's Most Powerful Healing Agent by Dr. Gutman and Stephen Schettini; and The Immune System Cure by Lorna Vanderhaeghe and Patrick Bouic

It seemed prudent to get myself off Paxil as quickly as possible! On September 8 2001, I reduced my Paxil dosage from 20mg to 10mg (1/2 pill) each day; at the same time, I increased my Whey protein intake by 20g/day taken in a glass of 1% milk at around 10:00pm each night. I decided to take the Whey protein just before bed in order to address another problem I've been having with high morning fasting blood glucose levels, which are typically 8mmol (144mg/dL) or more. Due to dizziness and lightheadedness I worked at home from September 10 to 14; otherwise, I had no other major withdrawal symptoms. On September 22, I reduced my Paxil dosage to 10mg (1/2 pill) every other day. For about a week, later in the day, usually between 3 to 5pm, I've been feeling very irritable for no apparent reason and my sense of balance seemed out-of-whack. My blood glucose levels were fine. My fasting blood glucose levels have been the lowest since I started recording them in January 2001. So the Whey protein seems to be effective in lessening the Paxil widthrawal symptoms (compared to my attempt early this year) and in reducing my fasting blood glucose levels.

Stopped Paxil completely on October 8 2001. For the past week I've been coughing, sneezing, and have a runny nose. Just coincidence? Probably! During the week, I've been feeling more nervous, jumpy and easily startled. I've also been feeling more irritable and emotional. For example, while watching For Love of the Game I felt like crying throughout the movie! And I'm not even very fond of baseball! I'm also finding my wife's attitudes towards me very annoying (I usually just quietly accept her attempt to control everything; her habit of minimizing the importance of my personal feelings, opinions, and advice; and her general overall negativity). Is this indicative that my normal feelings are returning after being suppressed for the past 15 months by Paxil? I also think I may also be overreacting to any attempts to control me and any kind of negative reactions towards me; both areas in which I have a past history of being particularly sensitive to!

Paxil experience summary

Paxil was prescribed by my MD (Dr Christina Mundi) on June 14 2000 to treat mood swings after I'd seen theraphist Sandra Slover, April 26 and May 11 2000, who recommended I take an anti-anxiety drug. Paxil belongs to a group of drugs known as selective serotonin reuptake inhibitors (SSRI). These medicines are thought to work by increasing the activity of the chemical serotonin in the brain. Takes a few weeks to work, can be very addictive, and should be stopped by reducing dose by 10%/week while supplementing with a high-bioavailable Whey Isolate protein such as Immunocal/HMS90 (which is very expensive). Side effects (experienced by me): decreased sexual desire; delayed ejaculation; increased sweating; trouble in sleeping; unusual tiredness and weakness. Withdrawal symptoms (experienced by me): easily agitated; dizziness and lightheadedness; headaches; inability to focus and concentrate; and inexplicable emotional outbursts. Feb01: Reduced from 20mg to 10mg. Feb12: Stopped. Experienced withdrawal symptoms listed above. Feb16: At the insistent promptings of my wife, and my own state of misery, started again at 20mg/day. Sep08: Reduced to 10mg/day (1/2 pill) while increasing ingestion of unsweetened SISU Body Elite Whey Protein Isolate from about 20 to 40mg/day. Sep29: Reduced to 10mg (1/2 pill) every other day. Oct08: Stopped Paxil completely but continued with Whey protein twice /day.

Glucokinase

What is glucokinase? This question was raised when I was trying to learn the potential benefits of using a Biotin supplement. I couldn't find a satisfactory answer and ended up being confused. However, I let my intuition guide me to add Biotin to my supplement regime and to investigate later why it might be beneficial. My investigation led me to glucokinase. According to my Gage Canadian Dictionary, "kinase is an enzyme able to activate the inactive form of another enyzme." So glucokinase is an enzyme. But what is an enzyme? I guess I need to bone up on words used by doctors and biochemists.

Glucokinase controls the rate of metabolism of glucose in pancreatic beta cells, and the metabolism rate is related the the amount of insulin secreted. A glucokinase gene mutation could cause the secretion of less insulin. Why? The first step in glucose metabolism is the phosphorylation of glucose to glucose 6-phosphate. In most tissues (for example, muscles), this first step is catalysed by hexokinase (HK), which has a low Km for glucose, and is inhibited allosterically by its product glucose 6-phosphate. In turn, inhibitation of HK suppresses glucose uptake. In the liver and pancreatic beta cells, phosphorylation of glucose to glucose 6-phosphate is catalysed by glucokinase. Glucokinase has a high Km for glucose and is not inhibited by glucose 6-phosphate. Glucokinase phosphorylates glucose only when blood glucose levels are high. Glucokinase plays a key role in the regulation of glucose-induced insulin secretion and it also determines the "set point" for insulin secretion.

Getting glucose into cells

Glucose entry into cells involves a family of glucose transporter proteins (GLUTs) which are structurally related but encoded by different genes.

• GLUT1 is used in many tissues; for example, muscle, brain, kidney, and colon
• GLUT2 is used in liver and pancreatic beta cells
• GLUT3 is used in the brain
• GLUT4 is used in skelital muscle and adipose tissue
• GLUT5 is the small intestine fructose transporter

Boning up...

Using my Webster's 9th Collegiate Dictionary for all definitions.

• Enzyme is "any of numerous complex proteins that are produced by living cells and catalyze specific biochemical reactions at body temperature."
• Glucokinase is "a hexokinase found especially in the liver that catalyzes the phosphorylation of glucose."

Hexokinase? Phosphorylation?

• Hexose is "any monosacchoride (eg, glucose) containing six carbon atoms in the molecule." Hexokinase is "any of a group of enzymes that accelerate the phosphorylation of hexoses (as in the formation of glucose-6-phosphate from glucose and ATP) in carbohydrate metabolism."
• Phosphorylate is "to cause (an organic compound) to take up or combine with phosphoric acid or a phosphorus-containing group."
• Phosphorylation is "the process of phosphorylating a chemical compund either by reaction with inorganic phosphate or by transfer of phosphate from another organic phosphate; especially the enzymatic conversion of carbohydrates into their phosphoric esters in metabolic processes."

ATP? Esters?

• ATP is "a phosphorylated nucleoside ... of adenine that supplies energy for many biochemical cellular processes by undergoing enzymatic hydrolysis especially to ADP."
• Ester is "any class of often fragrant compounds formed by the reaction between an acid and an alcohol usually with elimination of water."

ADP? Nucleoside? Adenine? Hydrolysis?

• ADP is "an ester of adenosine that is reversibly converted to ATP for the storage of energy by the addition of a high-energy phosphate group-called also adenosine diphosphate."
• Nucleoside is "a compound (as guanosine or adenosine) that consists of a purine or pyrimidine base combined with deoxyribose or ribose and is found especially in DNA or RNA."
• Adenosine is "a nucleoside...that is a constitituent of RNA yielding adenine and ribose on hydrolysis."
• Hydrolysis is "a chemical process of decomposition involving splitting of a bond and addition of the elements of water."

Purine? Pyrimidine? Deoxyribose? Ribose?

• Adenine is "a purine base ... that codes hereditary information in the genetic code in DNA and RNA."
• Purine is "a crystalline base...that is the parent of compounds of the uric-acid group ... a derivative of purine: especially a base (as adenine or guanine) that is a constituent of DNA or RNA."
• Deoxyribose is "a pentose suger ...that is a structural element of DNA."
• Ribose is "a type of suger made up of five carbon atoms to the molecule, instead of the six that make up glucose."
• RNA is ribose + nucleic acid that helps promote the synthesis of cell proteins.
• Pentose is "any monosaccharide...(as ribose) that contains five carbon atoms in the molecule."

Glycolysis

Planned future area of investigation...