Have you ever wished you could go back in time? Revisit the past, undo a mistake, make a different choice and see what how things might have turned out?
It’s usually when we’re facing a difficult obstacle
and realise we could have prevented it that thoughts like these come to mind. The onset of diseases like lung cancer or stroke are certainly among life’s more challenging obstacles, and often fill us full of regret: why didn’t we follow a different path when we had the chance? Why did we sit back and ignore reality, just waiting for disease to strike? Our regrets grow as we recall one lost opportunity after another, but it’s often too late to change course.
Sometimes, if we’re very lucky, the âwake-up call’ comes after a false alarm or an event that brings us to our senses. Just ask anyone who has narrowly escaped an accident or had a brush with death: it’s as if we suddenly see what life has in store for us. And it is precisely this ability to fast-forward into the future that sparks our awareness and makes us turn back.
The day Philippe confronted his diabetes
Philippe Lebon experienced this âlightbulb moment’ a few months ago, on a day just like any other for the 53 year-old diabetic accountant. As he did most evenings, Philippe came home from the office, exhausted from working overtime, smoked a cigarette in the garden while swearing at the dog barking next door, and went to see what was in his letterbox. Until then, nothing had pointed to this being the âlast day of his old life’. But when he opened the door, he came face to face with his daughter and son-in-law, greeting him with open arms. He hadn’t seen them for 18 months after they had left for South America! It was a truly emotional moment which only intensified when his daughter announced she was four months’ pregnant with a baby boy and that she and her husband had moved back to the area.
That night, Philippe couldn’t sleep. He tossed and turned, tormented by the unassailable fear that something might happen to him, that his grandson would never know his grandfather. Swirling around in his head were his doctor’s repeated warnings that his unhealthy lifestyle and diabetes were going to be the death of him
, that they would lead to a heart attack just as they had with his father, and his grandfather before him - who Philippe had never known. And yet he had done nothing about it. After all, he told himself, when your time’s up, it’s up. Nothing was going to stop him from enjoying what was left of life’s pleasures. That was his mantra when anyone brought up the health risks posed by his diabetes. But this time, it struck him as ridiculous. Maximising the chances of having a relationship with his grandson - he who himself had never had a grandfather, and of seeing the happiness on his daughter’s face: surely they were far more desirable pleasures?
The next morning, he decided to ask for some time off, with the firm intention of doing everything possible to take control of his diabetes
and to finally take proper care of himself. From now on, he would not only give up his bad habits, he would adopt good ones. He would lose weight, start exercising, eat healthily, stop smoking â¦ the list was long. In order to achieve it, he would listen to his doctor’s advice but would also explore other avenues. He would not simply accept recommendations passively, but would be master of his own fate. And to do that, he would familiarise himself with all the mechanisms of the disease that was eating away at him and which had so blighted his family.
What risks will Philippe be avoiding by changing his lifestyle?
To start with, Philippe wants to establish exactly what health risks he will be minimising by changing his lifestyle. Slowly but surely, he comes to understand the physiopathology of diabetes.
First, he discovers some alarming statistics:
- More than 12,000 diabetics are hospitalised each year for myocardial infarction (heart attack).
- More than 9,000 diabetics each year suffer amputation of a limb.
- Almost 3,000 new cases of terminal kidney failure are recorded each year among diabetics.
- Three-quarters of all diabetics will die from their disease. 1
Digging deeper, he learns that excess glucose in the blood gradually degrades the small blood vessels (arteries, veins, capillaries) resulting in damage to the eyes (diabetes is the leading cause of blindness) and kidneys, and above all, slow and inexorable degeneration of the nervous system
. We obviously hear less about these small blood vessels than large ones, damage to which results in inflammation of the coronary artery, myocardial infarction, inflammation of artery walls in the legs and high blood pressure. Philippe also realises his doctor was right: the risk of suffering one or more of these problems increases significantly if a family member has already been affected.
However, what Philippe didn’t realise was that diabetes can also havefatal consequences in the short term
. Defective insulin production in type 2 diabetes deprives cells of glucose, which then turn to another source of energy: fatty acids. This triggers the release of molecules that accumulate pathologically in the blood, making it acidic. This is called diabetic ketoacidosis and it can result in sudden diabetic coma
. Indeed, prior to the discovery of insulin in 1921, it proved fatal for diabetics within a matter of weeks.
Finally, Philippe comes to understand why he has always had such a strong urge to urinate and to drink almost constantly. His badly-damaged kidneys have gradually become overwhelmed by the amount of glucose they’ve had to filter. In âcoming to their rescue’, his body has been providing more and more fluid to lower the glucose concentration. Which is why Philippe had the very specific feeling that water simply flowed through his body without stopping â¦
One of the first things Philippe wants to know is why this disease has affected him. Is it really just down to his lifestyle choices?
Or is there an element of bad luck involved? The truth is, Philippe’s trying to absolve himself of some of the responsibility.
While the disease mechanisms of type 2 diabetes are not yet fully understood, what is known about them will do little to alleviate Philippe’s feelings of guilt.
He begins by learning about the origins of the disease. Glucose, which we get from food, is virtually the sole fuel for the brain, as well as being the muscles’ primary source of energy during physical exertion. Our cells also need it to function properly. After a meal, glucose circulates abundantly in the bloodstream causing pancreatic beta cells to release the hormone insulin. It is insulin that instructs our cells to store glucose as and when they need to (should they store it or use it to generate energy?).
But in type 2 diabetes, things don’t proceed as they should: insulin production is defective and cells respond incorrectly to the instructions from insulin. Elevated blood glucose levels therefore remain very high. The question is why pancreatic beta cells stop producing enough insulin and why muscle cells no longer respond properly to insulin.
When did things start to go wrong?
Philippe will of course discover that the picture is far from straightforward. A number of factors can influence the disease process, one of which will prove of particular interest to him.
When you are overweight like Philippe, fat-storing cells called adipocytes become enlarged. Excess fat causes metabolic stress which releases pro-inflammatory cytokines. These molecules have an immediate effect on the immune system, attracting macrophages which attack certain cells, including pancreatic beta cells. These random attacks gradually contribute to a decrease in insulin levelsâ¦
And that’s not all! The cells of visceral adipose tissue (especially around the stomach) constantly release large amounts of free fatty acids. This unintended flow stimulates glucose production from amongst others, muscle tissue, and interferes with blood glucose utilisation resulting in competition for oxidation between free fatty acids and glucose. Muscle energy is therefore provided first and foremost by oxidation of free fatty acids: glucose intended for the body’s cells builds up in the bloodstream. The pancreas gets to work to restore the balance by increasing insulin production in order to deliver blood glucose to cells: this is called hyperinsulinism. But in the long term, such overproduction exhausts the pancreas leaving it incapable of secreting the amounts of insulin needed to regulate blood sugarâ¦
Of course, Philippe knew he was too fat and had planned to go on a diet one of these days, but he never imagined it could have such an impact on his health. It’s true that people are never really told why being overweight is bad for them â they tend to be blamed rather than enlightened â¦
Berberine: how Philippe discovered a ’rare gem’
The complexity of diabetes’ mechanisms and the subtlety involved in regulating them makes developing effective drugs a real challenge. For the majority of the drugs available (and there are many!), potential benefits need to be evaluated against risks incurred; while insulin injections regulate all or almost all the mechanisms in type 1 diabetes, they are rarely effective in type 2 because cells are resistant to insulin.
Philippe spends a few months surfing the internet, consulting websites, diabetic communities, scientific studies, and opinions. He quickly learns how to spot those sites that exist only to sell products or peddle untruths. Drawing on his background as an accountant, he meticulously takes notes and compiles a genuine list of recommendations and âmust-dos’ for improving his diabetes.
This list obviously features the essentials: take some exercise, eat a balanced diet
, quit smoking, lose weight sensibly â¦ But it also includes supplementing with a natural product that to begin with, he was not sure even existed. From the outset, he had been keen to satisfy himself that the drugs his doctor wanted to prescribe for him were effective, and that there was no natural, safe and worthwhile alternative. It was important to him that the efficacy of any alternative should be scientifically validated, and that he himself should feel the benefits once he’d tried it. It didn’t take him long to find such a product and even less time to start taking it. Here’s what he found out about berberine
, the ârare gem’ that has helped him fight his diabetes and live to be the grandfather he is today â¦
Berberine is the major component of a traditional Chinese herb (Rhizoma Coptidis) and has been used for hundreds of years - for its anti-inflammatory properties 4
. Diabetes in humans is a very recent development and berberine’s blood glucose-lowering effect was only discovered by chance in 1988.
Berberine is able to lower blood sugar â both fasting and post-prandial
, and glycated haemoglobin (HbA1c). It is as effective as metformin
, one of the most commonly-prescribed drugs for diabetes (marketed under the brands Glucophage, Stagid and their generic names) 5
It improves insulin sensitivity and aids weight loss in people with type 2 diabetes6,7
Mechanisms of action
Rather than directly stimulating the pancreatic beta cells which secrete insulin 8
, berberine’s effects on cell insulin sensitivity appear to step from improvements to the glucose transporters (GLUT1) 9-10
present on the cell’s surface. It is also known to activate AMPK, an enzyme which contributes to the coordinated regulation of energy metabolism, dietary intake and tissue sensitivity to insulin 11-14
. As a result of this property, berberine also offers a degree of protection against cardiovascular disease.
It inhibits alpha-glucosidase, an enzyme in the intestine which reduces carbohydrate absorption sup>15.
It regulates a number of lipogenic genes (PPARð
, SREBP-1c, AP2â¦) so reducing the accumulation of visceral fat 16-18
Berberine is recognised as safe at doses of up to 2g a day. No unwelcome side effects have been reported in research studies.
Today, Philippe adheres strictly to the instructions carefully recorded in his notebook. He has lost weight, now eats healthily, has quit smoking (though he has compensated for this nasty habit by chewing liquorice), has a better understanding of his blood tests, and has earned praise from his doctors. Most importantly, he has discovered a new pleasure in life: spoiling his grandson (
1. A. Fagot-Campagna, I. Romon, S. Fosse, C. Roudier. Prévalence et incidence d udiabète, et mortalité liée au diabète en France â Synthèse épidémiologique. Saint-Maurice (Fra) : Institut de veille sanitaire, novembre 2010, 12 p.
4. Huang lian. Chinese materia medica dictionary. Shangai : Shangai Scientific & Technical Publishers ;1986, p 2022-30.
5. Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004 ;10 :1344-51.
6. Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008 ;93 :2559-65.
7. Yin J, Chen M, Tang J, Li F, Zhou L et al. Effects of berberine on glucose and lipid metabolism in animal experiment. Chin J Diabetes 2004 ;12 :215-8.
8. Zhou J, Zhou S, Tang J et al. Protective effect of berberine on beta cells in streptozotocin and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 2009 ;606 :262-8.
9. SH Kim, EJ Shin, ED Kim, T Bayaraa, SC Frost, CK Hyun. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biol Pharm Bull, 30 (2007), pp. 2120â2125
10. A Cok, C Plaisier, MJ Salie, DS Oram, J Chenge, LL Louters. Berberine acutely activates the glucose transport activity of GLUT1. Biochimie, 93 (2011), pp. 1187â1192
11. DG Hardie. AMP-activated protein kinase: a master switch in glucose and lipid metabolism. Rev Endocr Metab Disord, 5 (2004), pp. 119â125
12. Z Cheng, T Pang, M Gu, AH Gao, CM Xie, JY Li, et al. Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK. Biochim Biophys Acta, 1760 (2006), pp. 1682â1689
13. SH Kim, EJ Shin, ED Kim, T Bayaraa, SC Frost, CK Hyun. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biol Pharm Bull, 30 (2007), pp. 2120â2125
14. J Yin, Z Gao, D Liu, Z Liu, J Ye. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab, 294 (2008), pp. E148âE156
15. GY Pan, GJ Wang, JG Sun, ZJ Huang, X.C. Zhao, Y Gu, et al. Inhibitory action of berberine on glucose absorption. Acta Pharm Sin, 38 (2003), pp. 911â914
16. C Huang, Y Zhang, Z Gong, X Sheng, Z Li, W Zhang, et al. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun, 348 (2006), pp. 571â578
17. BH Choi, IS Ahn, YH Kim, JW Park, SY Lee, CK Hyun, et al. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp Mol Med, 38 (2006), pp. 599â605
18. LB Zhou, MD Chen, X Wang, HD Song, Y Yang, JF Tang, et al. Effect of berberine on the differentiation of adipocyte. Chin Med J, 83 (2003), pp. 338â340