November is National Diabetes Awareness Month. It therefore timely to consider what diabetes actually is, why we should care, and how it can be treated. Diabetes, or more technically, diabetes mellitus, now affects 10% of Canadians, with the numbers increasing annually, not only in Canada but worldwide. There are several forms of diabetes, the most prevalent of which are 鈥楾ype 1鈥�, an autoimmune disease in which the insulin producing beta cells in the pancreas are destroyed, and 鈥楾ype 2鈥�, wherein subjects are both resistant to the actions of insulin and are unable to produce sufficient insulin to overcome that resistance. However, the majority of people with diabetes have Type 2 (~90%), as compared to those with Type 1 (~10%). Other forms of diabetes include Gestational, which affects pregnant women and is a risk factor for later development of Type 2 diabetes, as well as several rare mono-genetic diseases.
Both Type 1 and Type 2 diabetes have a strong genetic component, with family history being a significant risk factor. Some individuals also have higher risk based on their race, most notably people of African, Arab, Asian and South Asian, Hispanic or Indigenous descent. However, interaction with the environment also plays a significant role in the development of Type 2 diabetes, in particular. Hence, being overweight or obese is a significant risk factor for the development of Type 2 diabetes, with ~85% of people with Type 2 diabetes being overweight or obese.
Overweight and obesity contribute to the risk for Type 2 diabetes by reducing the ability of cells to take up a key sugar, glucose, from the blood in response to insulin, called insulin resistance. This can be caused in a number of ways, although the production of inflammatory hormones by the increased fat mass in overweight/obesity being a significant factor. The net effect is an increase in blood glucose levels which, in turn, exerts a demand on the pancreatic beta cells to produce more insulin. If the beta cells can 鈥榬ise to the challenge鈥�, near-normal blood glucose levels are maintained. However, when the beta cells are unable to produce sufficient insulin, then diabetes results, as characterized by blood glucose levels of greater than 7 mM in the fasting state and greater than 11.1 mM after eating (the normal values are 4-6 mM and 5-7 mM, respectively). Unfortunately, chronic increases in blood glucose levels are associated with a number of serious problems. According to Diabetes Canada, long-term elevated glucose causes 30% of strokes, 50% of kidney failure requiring dialysis, 70% of non traumatic leg/foot amputations resulting in a 5- to 15-year reduction in life span. Diabetes is also thea leading cause of blindness in Canada,.
Fortunately, there are now many treatment options for people with Type 2 diabetes, depending on their levels of blood glucose. Notably, one factor in the blood, hemoglobin A1c (HbA1c) is used as a marker of blood glucose levels over the preceding 3-month period. These guidelines can be found on the .
In brief, if HbA1c levels are above normal but still relatively low, then diet and exercise can be prescribed, both of which help to reduce blood glucose and body weight, therefore also decreasing 鈥榩ressure鈥� on the beta cell. However, if HbA1c levels are high and/or diet and exercise do not reduce blood glucose levels sufficiently, then metformin can be prescribed, which acts to reduce the production of even more glucose by liver. Finally, depending on other risk factors, such as existing cardiovascular and/or kidney disease, a variety of different therapeutic options are available, alone or in combination, including: glucagon-like peptide-1 receptor agonists (GLP-1RA: to stimulate the beta cells, reduce body weight and provide cardioprotection), sodium-glucose luminal transporter 2 inhibitors (SGLT2i: to induce loss of blood glucose through the urine and provide cardioprotection), dipeptidylpeptidase 4 inhibitors, sulfonylureas and meglitinides (to stimulate the beta cells) and thiazolidines (to increase the sensitivity of cells to insulin). Finally, if combinations of these treatments fail to adequately reduce blood glucose levels, then insulin becomes the treatment of choice.
One question that is frequently asked is whether diet and exercise alone can prevent Type 2 diabetes. In a landmark clinical trial in 2002 from the US Diabetes Prevention Program Research Group, over 3000 people with pre-diabetes were randomized to either no-treatment, metformin or intensive lifestyle modification (i.e., a monitored diet and exercise program), and their HbA1c levels were followed for up to 4 years. The cumulative incidence of diabetes in the lifestyle group (20%) was lower than found in the metformin (29%) and untreated (37%) groups. Similarly, the 2006 Finish Diabetes Prevention Study and the 2008 China Da Qing Diabetes Prevention Study showed that intensive lifestyle modification over a period of up 6 years reduced the progression to Type 2 diabetes by 43-51%. Importantly, very recent data from the English National Health Service Diabetes Prevention Programme (2023) now shows that the findings from the clinical trials can be recapitulated in the real-world.
Unfortunately, none of the lifestyle intervention programs was successful in completely preventing the onset of Type 2 diabetes, although all of the programs delayed development of the disease. This is likely due, at least in part, to the progressive nature of Type 2 diabetes, caused by increasing loss of the insulin-producing beta cells over time. It is also worth noting that optimal intensive lifestyle modification requires great effort on the part of the individuals, along with the participation of a professional team to tailor the diet and exercise regimens to each patient, making long-term compliance difficult. However, the more years that an individual remains diabetes-free, the lower the risk of long-term complications, as well as of the associated burden to both the patient and the health care system. Furthermore, maintaining good dietary practises as well as a healthy body weight through exercise are associated with other benefits, including cardiovascular health. Who can argue against that?
Patricia Brubaker, Ph.D., F.R.S.C., F.C.A.H.S. is a Professor Emerita, Departments of Physiology and Medicine and a Banting & Best Distinguished Scholar at the University of Toronto, Toronto, ON, Canada. Dr. Brubaker completed both her undergrad and PhD at 不良研究所.
