Bongiwe Nkondo expands on the four hormones needed for glucose control: insulin, amylin, incretins and glucagon.

Glucose, also known as blood sugar, is the preferred source of energy by the body cells. It’s transported from the liver or intestines to the cells of the body through the bloodstream. The body has a system that regulates the glucose level so that it doesn’t rise too high or drop too low, as this has detrimental health complications.

The regulation of glucose is done through an intricate system, involving various hormones insulin, amylin, incretins and glucagon.

Blood glucose regulation 101

When glucose levels are higher than normal (hyperglycaemia), the hormone, insulin, is released from the pancreas and this allows the glucose circulating in the blood to be taken up by the body cells and also to be used to create fat cells. This restores the blood glucose to a normal level (euglycaemia).

When the glucose levels are lower than normal (hypoglycaemia), the hormone, glucagon, is released and then the glycogen in the liver is broken down and converted into glucose, restoring euglycaemia.

The four hormones

Insulin

Insulin is a hormone secreted by the beta cells of the pancreas. It’s carefully regulated in response to circulating blood glucose levels. It allows body cells to access glucose for energy and it’s also involved in the creation and storage of fat.

Insulin isn’t secreted if the blood glucose level is less than or equal 3,3mmol/L, but is released if the amount is higher and increases as blood glucose levels increase.

After eating, insulin is released in two phases: an initial rapid release of preformed insulin, followed by an increased secretion by the pancreas and subsequent release in response to the blood glucose levels. There is a long-term release of insulin if the blood glucose levels remain high.

While glucose is the most potent stimulus of insulin release, there are other factors that also stimulate the creation and release of insulin, like certain amino acids, such as arginine, leucine, lysine, and glucagon-like peptide 1 (GLP-1) after a meal, to name a few.

So, how does it regulate blood glucose? When your glucose levels are increased, insulin is released. The insulin allows glucose entry into the muscles and liver, converting glucose to glycogen for storage and the remainder of the glucose is converted into fat cells. Hence, glucose is removed from the blood, restoring the glucose level to normal.

Amylin

Amylin is also a hormone which regulates blood glucose levels and is secreted by the pancreas alongside insulin. It complements the effects of insulin by reducing the blood glucose level after meals and by suppressing the creation of glucagon (which would work to increase blood glucose levels).

In Type 1 diabetes, the secretion of amylin is also deficient. Amylin also helps to slow down gastric emptying, the process by which the contents of the stomach are moved or emptied into the small intestine, and therefore slowing the rate of absorption of nutrients by the small intestine.

Incretins

These are hormones made by the digestive tract and includes GLP-1. They increase the amount of insulin released by the pancreas after eating, even before blood glucose levels become elevated. They also slow down the rate of absorption of glucose in the blood by reducing the rate of gastric emptying/digestion and may directly reduce food intake. Incretins also inhibit the release of glucagon from the alpha cells of the pancreas.

Glucagon

Glucagon is a hormone released by the alpha cells of the pancreas. It’s released in different circumstances: when the blood glucose level is low (hypoglycaemia), or when there are increases in adrenaline and epinephrine when you feel threatened or your body is under stress (fight or flight mode), and due to other factors.

When glucagon is released, the liver converts glycogen (sugar previously assimilated and stored) into glucose, thus raising the blood glucose level and restoring a balance.

Work with a multi-disciplinary team

The body is so intricate and complex. Each organ, hormone and substance play such a crucial role in maintaining balance. Glucose control is reached through the harmonious work of the different elements. When one element is off balance, it has an effect on the balance of the overall system, as seen in diabetes. Therefore, it’s best to work with a multi-disciplinary team to ensure you have the necessary tools to create balance in your body.

References

1. Holst JJ et al. (2021). The Role of Incretins on Insulin Function and Glucose Homeostasis. Endocrinology 162(7): 1 – 10.
2. Dong XL et al. (2018). Influence of blood glucose level on the prognosis of patients with diabetes mellitus complicated with ischemic stroke. Journal of Research in Medical Sciences23:10
3. Mayan KL, Raymond JL. (2017). Krause’s Food and the Nutrition Care Process.14^th Elsevier: Missouri.
4. Stephen LA et al (2004). Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. Diabetes Spectrum 17(3): 183 – 190.

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Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. It’s important to follow the five point treatment plan to decrease developemnt.

The kidney is a vulnerable organ as well as the most important target of microvascular damage in both Type 1 and Type 2 diabetes.

The first description of the association between diabetes and kidney damage in humans was in 1552 BC.² As the disease spectrum has changed around the world, diabetic kidney disease (DKD) has become the single most frequent cause of end-stage kidney disease.

Kidney involvement both directly and indirectly increase involvement of other organs especially the heart and eye, and increase morbidity and mortality in diabetic patients.

The overall incidence 20 years after the diagnosis of diabetes is approximately 4 to 17% and after 30 years is about 16%. According to some studies the incidence of kidney disease in Type 1 diabetes is decreasing. The main reason for that is early diagnosis of Type 1 diabetes and good control of hyperglycemia.¹

In Type 2 diabetes. the kidney damage may be present at the time of diagnosis. This is why it’s so important to screen people susceptible to Type 2 diabetes regularly for abnormal glucose values.

Genetics

Many patients with long-term high glucose have no diabetic kidney disease while others with a short disease course have clinical diabetic kidney disease (nephropathy). This may be due to predisposing factors including genetics.

The risk of diabetic kidney disease increases in Type 1 and Type 2 diabetes if the patient has a history of diabetic kidney disease in one of their first-degree relatives.

Patients living with diabetes who have a family history of hypertension or heart disease are more likely to develop diabetic kidney disease.

Screening

The easiest screening method is to evaluate a urine sample. This can be done in a doctor’s office with a urine dipstick. If this is normal, the urine sample should be sent to a laboratory for a urine albumin-creatinine ratio test.

Natural course of diabetic kidney disease

First stage

The filtration through the kidney tubes, called glomeruli, increases and the kidney enlarge. The urine albumin-creatinine ratio is still normal and blood pressure is also normal.

Second stage: microalbuminuria

With the progression of kidney involvement, urine albumin-creatinine ratio will also increase. This stage is called hidden or subclinical kidney disease.

In this stage, the conventional urine test strip in the doctor’s rooms will be negative but the risk of heart disease starts to increase. With Type 1 diabetes, the prevalence of other microvascular (small vessel) diseases start to increase, such as the eye and the feet. With Type 2 diabetes, other factors, such as age, high cholesterol, high blood pressure and duration of disease, play a role to increase microalbuminuria (small proteins in urine).

Diagnosis at this stage is a very good opportunity to prevent progression to clinical kidney disease.

Third stage: macroalbuminuria

This stage is also called diabetic kidney disease or clinical nephropathy. It occurs about 10 to 20 years after onset of diabetes; about five to 10 years after the onset of microalbuminuria.

In this stage, heart disease and strokes also increases compared to the previous stage, and about 75% of patients have high blood pressure. Control of blood pressure in Type 2 diabetes with previous hypertension becomes more difficult.

The conventional dipstick test in the doctor’s rooms is positive for proteins. Due to the leaking of proteins in the urine, these patients can develop swelling of the legs. If the leaking of proteins increases more the swelling can also develop around the eyes.

Fourth stage: End stage kidney disease

The end stage of kidney disease is reached about 10 years after the onset of clinical kidney disease (stage 3). The risk of heart disease and stroke increases, and the incidence of foot ulcers are also increased.

The prevalence of Type 2 diabetes to develop end stage kidney disease is nine times higher than Type 1 diabetes.

Diagnosis

To prove the diagnosis of diabetic kidney disease, the following criteria is used:

• Enough time. At least 10 years past the onset of diabetes but this may be shorter in Type 2 diabetes.
• Persistent proteins in urine more than 300mg in 24 hours ( normal is less than 30mg per 24 hours).
• Diabetic retinopathy (eye disease) at the same time.

There are other causes in diabetes that can also lead to kidney disease:

• Uncontrolled blood pressure
• Recurrent bladder infections
• Increased cholesterol with renal artery stenosis (decreasing of blood flow to the kidney)

Five point treatment plan

Treatment is based on the following principles:

• Tight control of glucose

Keep the HbA1c (3 month average blood glucose) below 7% and in patient with glucose sensors; keep the time in range (time between 4 and 10 mmol\L in 24 hours) more than 70%.

• Control of blood pressure

Both high glucose and high blood pressure can progress to kidney disease. In the control of blood pressure, it’s important to use the correct drug that address the kidney function as well. The renin-angiotensin-aldosterone system inhibitors can reduce the progression of diabetic kidney disease. There are two groups in this class: ACE inhibitors (perindopril or enalapril) and ARB group. (valsartan or losartan).

• Restriction of protein intake

High protein intake increases the filtration of blood through the kidney. Protein restriction can decrease the progression of kidney disease

• Stop smoking

• Manage cholesterol

The aggressive treatment of abnormal lipids reduce both microvascular (small vessel disease such as eye, kidney and feet) and macrovascular disease (heart attack and stroke). The therapeutic target for LDL cholesterol (bad cholesterol) is below 1,8 mmol/L.

New drugs

The use of the ACE and ARB drugs was up to 2016 the only drugs, except cholesterol lowering medications, that could slow diabetic kidney disease.

There are now two new drugs available in SA that decrease the progression of diabetic kidney disease by 30%. These drugs are from the class sodium glucose transporter 2 inhibitor (SGLT2i) and work in the upper part (proximal tubuli) of the kidney. The reabsorption of glucose and salt are blocked. This leads to glucose in the urine and due to this: weight loss, decrease of blood pressure and improvement of kidney function are seen. The two available drugs in RSA are dapagliflozin and empagliflozin.

Final thought

Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. It’s important to follow the five-point treatment plan to decrease the chance to develop the disease, and should it already be present to use the correct drugs to decrease the progression of the disease.

Reference:

1. Bojestig M et.al. “ Declining incidence of nephropathy in insulin dependent diabetes mellitus.” N Engl J Med 1994;330: 15-18
2. Cameron J.S. 2006 “The discovery of diabetic nephropathy: from small print to centre stage.” Journal of Nephrology 19 ( Suppl 10): S75-S87

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