The Diabetes Code. Dr. Jason Fung

      HYPERGLYCEMIA, OR HIGH blood glucose, characterizes all forms of diabetes. When blood glucose levels rise above the kidney’s ability to reabsorb the glucose (the renal threshold), it spills over into the urine, causing frequent, excessive urination and severe thirst. The chronic loss of glucose may lead to rapid weight loss and also stimulate the appetite. The most typical symptoms seen in diabetes therefore include

      •increased thirst,

      •frequent urination,

      •rapid, unexplained weight loss,

      •increased hunger despite weight loss, and

      •fatigue.

      These symptoms of hyperglycemia are common to all forms of diabetes, but they occur more frequently in type 1 diabetes, since the onset of type 2 diabetes is typically very gradual. Today, type 2 diabetes is most often diagnosed during routine blood testing, before patients have symptoms.

      In severe cases, patients—typically those with type 1 diabetes—may present with diabetic ketoacidosis. Dangerously high levels of acid build up in the blood due to the severe lack of insulin. Symptoms include confusion, rapid breathing, abdominal pain, a fruity smell to one’s breath, and loss of consciousness. This is a true emergency situation, which needs immediate treatment with insulin.

      Severe cases of type 2 diabetes may present with hyperosmolar non-ketotic syndrome. High blood glucose stimulates excessive urination, leading to severe dehydration, seizures, coma, and even death. Since insulin levels are normal or high in type 2 diabetes, ketoacidosis does not develop.

       DIAGNOSING DIABETES

      DIABETES MAY BE diagnosed by one of two blood tests: the hemoglobin A1C (often abbreviated to A1C) or the blood glucose. The A1C, which has been accepted as a diagnostic criterion by the American Diabetes Association since 2009, is the most convenient screening test for diabetes because it does not require fasting and can therefore be done at any time of the day.

       Hemoglobin A1C

      HEMOGLOBIN IS A protein found inside red blood cells that carries oxygen to the entire body. Over the average three-month lifespan of a red blood cell, glucose molecules attach to the hemoglobin in proportion to the prevailing blood glucose levels. The amount of glucose attached to the hemoglobin can be measured with a simple blood test called the hemoglobin A1C. The A1C thus reflects the body’s average level of blood glucose over three months.

      In North America, the A1C is given as a percentage, while in the U.K. and Australia, the units are expressed as mmol/mol. The American Diabetes Association defines an A1C level of 5.7 percent or less to be normal. A level above 6.5 percent is considered diabetic (see Table 2.2).

Table 2.2. Classification of diabetes and prediabetes according to A1C blood glucose levels

A1C	Classification
< 5.7%	Normal
5.7%–6.4%	Prediabetes
> 6.5%	Diabetes

      Prediabetes is the in-between stage, where blood glucose levels are abnormally high, but not quite high enough to be considered diabetic. It denotes a state of very high risk of future progression to full-fledged type 2 diabetes. A patient with a baseline A1C of 6.0–6.5 percent (42– 48 mmol/mol) has an estimated 25–50 percent risk of developing diabetes within five years. That’s more than twenty times the risk of a person with an A1C of 5.0 percent (31 mmol/mol).²

       Blood glucose

      THE SECOND TEST to diagnose diabetes is the blood glucose test, which is also known as the blood sugar or plasma glucose test. It is measured using either a fasting blood sugar test or an oral glucose tolerance test (OGT).

      For the fasting blood glucose test, a patient is asked to have no caloric intake for at least eight hours. A blood sample is then taken and the amount of glucose in the blood is measured. A level above 7.0 mmol/L (or 126 mg/dL) is considered diabetic.

      For the OGT, a patient is asked to ingest a standard test dose of 75 grams of glucose. A blood sample is taken two hours later and the amount of glucose in the blood is measured. A level above 11.1 mmol/L (or 200 mg/dL) is considered diabetic.

      The A1C has largely replaced the fasting blood glucose test and the OGT for diagnosis because of its simplicity and convenience, but all of these tests are considered accurate and acceptable. Occasionally, diabetes is diagnosed using a random blood sugar test. A blood sample is taken at a random time and the level of glucose in the blood is measured. A level above 11.1 mmol/L (or 200 mg/dL) is considered diabetic if accompanied by other symptoms.

      Table 2.3 Diagnostic criteria for diabetes

Fasting blood glucose > 7.0 mmol/L (126 mg/dL)

2 hour blood glucose > 11.1 mmol/L (200 mg/dL) during OGT

A1C > 6.5% (48 mmol/mol)

Symptoms of hyperglycemia and random blood glucose > 11.1 mmol/L (200 mg/dL)

      The total amount of glucose circulating in the blood at any time is surprisingly small—roughly a single teaspoonful. Glucose does not float freely around in the blood. Rather, most of the body’s glucose is contained within our cells.

      Hormones tightly regulate our blood glucose to avoid excessively low or high levels. Even when we eat large amounts of sugar, the blood glucose level still remains within a remarkably narrow, controlled range due to the coordinated actions of various hormones. As glucose is absorbed through the intestines into the blood, the islet cells within the pancreas secrete the hormone insulin. Insulin allows the glucose to enter the cells as fuel for energy. The body stores any excess glucose in the liver for future use, which keeps our blood glucose from rising out of its normal range.

       TYPE 1 DIABETES: THE FACTS

      TYPE 1 DIABETES has been previously called juvenile diabetes, since its onset commonly occurs during childhood. However, although three-quarters of all cases are diagnosed in patients under eighteen, it may present at any age. The global incidence of type 1 diabetes has been rising in recent decades for unknown reasons and may be increasing by as much as 5.3 percent annually in the United States.³ In Europe, at present rates, new cases of type 1 diabetes will double between 2005 and 2030.

      Type 1 diabetes is an autoimmune disease, meaning that the body’s own immune system damages the cells that secrete insulin. The patient’s blood contains antibodies to normal human islet cells, which provides evidence of an autoimmune attack. Over time, cumulative destruction of the insulin-producing cells causes type 1 diabetes to progress to severe insulin deficiency, whereupon symptoms typically occur.⁴

      There is a strong genetic predisposition to type 1 diabetes, but what eventually triggers the autoimmune destruction is uncertain. Seasonal variation in diagnosis may point to an infectious trigger, but which specific one is unclear. Other environmental agents that may play a role include sensitivity to cow’s milk, wheat protein, and low vitamin D. Type 1 diabetes often occurs together with other autoimmune diseases, such as Graves’ disease (which affects the thyroid) or vitiligo (which affects the skin).

      Type 1 diabetics suffer from a severe lack of insulin. Therefore the cornerstone of successful treatment is adequate replacement of the missing hormone insulin. The discovery of insulin injections dramatically improved the prognosis, leading to a widespread feeling that diabetes had been cured. However, the story did not end happily ever after. Over the long term, type 1 diabetics are at much higher risk of complications, which affect almost all organs of the body, than nondiabetics. Type